Chromatin Structure and Function


Brian Strahl is a Professor of Biochemistry and Biophysics at The University of North Carolina at Chapel Hill (UNC). His lab has been studying the role of histones and their post-translation modifications in chromatin structure and function - with an emphasis in cancer biology and gene regulation.  At UNC, Strahl provides instruction to undergraduate, graduate, and postdoctoral students in his laboratory.  Brian Strahl is also the Vice Chair in the Department of Biochemistry & Biophysics, and is the Faculty Director of the UNC High-Throughput Peptide Synthesis and Array Core Facility.  Over the years, Dr. Strahl has received a number of important awards for his work in the field of gene expression. In 2009, he received the Ruth and Phillip Hettleman Prize for Artistic and Scholarly Achievement from UNC. In 2008, the National Institutes of Health awarded him a EUREKA (Exceptional, Unconventional Research Enabling Knowledge Acceleration). His alma mater, the University of North Carolina at Greensboro, awarded him a Young Alumni Award in 2006 for scientific achievement. Brian Strahl has also won the ASBMB Schering-Plough Research Institute Award, a major biomedical award. In 2003, Brian Strahl was honored by the White House for his achievements and was awarded a Presidential Early Career Award for Scientists and Engineers. In 2004, Strahl was a PEW Scholar in Biomedical Sciences. Brian Strahl is a member of several professional organizations, including the American Society for Microbiology and the American Society of Biochemistry and Molecular Biology. 

Research Objectives

  • Histone Post-translational Modifications and the Histone Code

The Strahl lab is focused on understanding how a class of proteins called histones compacts our genetic information (DNA) and how these proteins contribute to the regulation of functions associated with DNA (gene regulation, DNA replication and DNA repair for example).  Histones are post-translational modified with a wide number of chemical modifications or "tags" (such as acetylation, methylation, and phosphorylation).  How they all contribute to chromatin (DNA/Histone) organization and function is not well understood, but many studies suggest they work in the form of a ‘histone code’ to regulate these events.  Brian Strahl’s lab is working on understanding how histone modifications functions (singly and in combination) using a number of distinct platforms (proteomics, etc.) and model systems (yeast and humans).  

Work History

Work History
Jan 2016 - Present

Vice Chair

Department of Biochemistry & Biophysics
Apr 2015 - Present

Co-director of the UNC Program of Chromatin and Epigenetics

Jan 2010 - Present

Faculty Director of the High-Throughput Peptide Synthesis and Arraying Facility (HTPSA), UNC School of Medicine

UNC School of Medicine

The UNC HTPSA Facility provides researchers with high quality services for peptide synthesis, purification, and characterization of synthetic peptides and preparation of custom designed peptide arrays.

Jan 2010 - Dec 2015

Director of Graduate Studies

UNC Department of Biochemistry

Awards and Honors

2009                            Recipient of the Ruth and Phillip Hettleman Prize for Artistic and Scholarly Achievement, UNC

2008                            Recipient of an Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) award from the NIH

2006                            Named as a Jefferson-Pilot Fellow in Academic Medicine, UNC

2006                            Recipient of the University of North Carolina at Greensboro Young Alumni Award
2005                            Recipient of the North Carolina State University Outstanding Alumnus Award

2005                            Recipient of the ASBMB Schering-Plough Research Institute Award for outstanding research contributions to biochemistry and molecular biology

2004                            Pew Scholar (Pew Scholars Program in the Biomedical Sciences)

2003                            Recipient of a Presidential Early Career Award for Scientists and Engineers  (PECASE)

2002                            Recipient of a UNC Research Council award

1999-2002                   National Institute of Health postdoctoral NRSA fellowship award

1998                            Recipient of the Becton-Dickinson award for outstanding research in Biochemistry (from Ph.D. thesis)

1993                            Recipient of the American Institute of Chemist Foundation award for being an outstanding senior student majoring in chemistry.

Professional Experiences

2015-present              Editorial board member of Journal of Biological Chemistry

2014                            Ad-hoc reviewer for Genes, Genomes, and Genetics (GGG) study section (Special Emphasis Panel ZRG1 GGG Q), NIH

2013-present              Editorial board member of Epigenetics & Chromatin

2012                            Ad-hoc reviewer for the NIH transformative research award initiative (Special Emphasis Panel ZRG1 BCMB-A), NIH

2012                            Ad-hoc reviewer for the NIH Director’s Early Independence Award (Special Emphasis Panel ZRG1 BBBP-E), NIH

2009-present              Editorial board member of Molecular and Cellular Biology

2008                            Ad-hoc reviewer; Fungal Genetics Special Emphasis Panel, NIH

2006                            Ad-hoc review panel member for NIDA Study Section, NIH

2005                            Ad-hoc review panel member for MG-C Study Section, NIH

Strahl lab Research Interests

Background – The genetic blueprint of life occurs in the form of DNA, which is faithfully packaged within the nucleus of each cell in our body.  DNA packaging, and its organization in the nucleus, is regulated by a class of proteins called histones.  These proteins create individual histone-DNA complexes, referred to as nucleosomes, which are further folded into higher-order chromatin structures that are poorly defined (Figure 1). It is therefore significant to ask: (i) how do distinct chromosomal domains such as “euchromatin” and “heterochromatin” become established and maintained, and (ii) how is the underlying DNA within this highly compact and repressive chromatin environment made accessible to the protein complexes that utilize it?  Our lab is addressing these questions by taking advantage of multiple model organisms and through applying a combination of genetic, biochemical and high-throughput proteomic approaches.

One mechanism that has emerged as a major regulator of the organization and function of chromatin are histone post-translational modifications (PTMs). Surprisingly, a vast number of covalent modifications, such as acetylation, methylation, ubiquitylation and phosphorylation exist on histones.  Numerous studies indicate that these modifications work together in the form of a ‘histone code’ to regulate chromatin-based activities.  This code (which David Allis and I introduced when I was a postdoc in his lab), is thought to functions through the direct recruitment of protein modifiers to the sites of modification, which then alter the organizational state of chromatin and/or facilitate a biological process (e.g. transcription). A famous example is the recruitment of HP1 (heterochromatin protein 1) to histone H3 that is methylated at lysine 9, resulting in the formation of highly compact, transcriptionally inert heterochromatin in cells (Figure 2).


Research areas in the lab:

I. Histone modifications in RNA polymerase II transcription – Of the known histone modifications, histone methylation and ubiquitylation have recently received much attention and are only now becoming understood.  Recent insights indicate that these modifications play a fundamental role in the organization of chromatin and in the activation and repression of genes controlled by RNA polymerase II.  We and others have found, for example, that a variety of enzymes which either methylate (e.g. Set1 and Set2) or ubiquitylate (e.g. Rad6) histones, associate with RNA polymerase II during the elongation cycle of transcription.  While Set2 associates directly with the C-terminal domain of RNA polymerase II, Rad6 and Set1 associate with the polymerase through an interaction with the PAF transcription elongation complex (Figure 3).  This finding indicates that histone modifications play a fundamental role in the transcription process. We seek to understand how these enzymes and their modifications regulate chromatin-based transcription and how defects in these processes result in diseases such as cancer.

One major focus of our lab is the histone methyltransferase Set2.  We have shown that this enzyme “travels” with RNA polymerase II down genes to mediate histone H3 lysine 36 methylation (Figure 4).  The function of this enzyme remained elusive until recent work showed that the methylation by Set2 recruits a histone deacetylase complex (Rpd3S) to the bodies of genes.  As it turns out, RNA polymerase II transcription involves the recruitment of histone acetyltransferases that function to help disrupt nucleosomes in front of the polymerase.  Set2’s function therefore is to recruit a histone deacetylase enzyme that restores the acetylation levels to their previous state after the passage of the polymerase.  Without this mechanism, acetylation levels remain high in the coding region and cryptic transcription start sites are inappropriately used.

To study histone modifictaions in gene regulation, our lab is using budding yeast as a model organism.  This organism provides a fantastic opportunity to employ both biochemistry and genetics to solve complex problems.  For example, we can easily mutate the histones and chromatin-modifying enzymes we study and examine how their mutation affects chromatin organization, transcription and other biological processes.  We can also insert affinity purification tags on any protein at will to study who they are associated with and where they occur in the genome (and if they get recruited to various ‘marks’).  Thus, this powerful organism affords a unique opportunity to study the fundamentals of chromatin modifications.  Significantly, most, if not all, of the enzymes and modifications we study in yeast are conserved in humans.  Thus, what we learn in yeast is directly applicable to how these enzymes operate in human cells, which is relevant as many of these enzymes have been associated with various human diseases including cancer.


II. High-thoughput proteomics and studies into the ‘histone code’ – More recently, our lab has been engaged in a large-scale, high-throughput proteomics project to uncover the function of histone modifications using peptide arrays.  My interest in this stems from the fact that as a postdoc in David Allis’ lab, we proposed the ‘histone code’ hypothesis to explain how distinct covalent histone PTMs might work together to regulate epigenetic inheritance, gene expression and the control of cell growth, differentiation and disease.  However, progress in this area has been slow due to the lack of new tools to study it.  Because of this, we set out to develop a novel ‘histone code’ peptide array platform to explore this critical question in chromatin biology (Figure 5). Since initiating this project, we have shown how a number of effector proteins are influenced by combinatorial histone PTMs.  We are also collaborating with a wide number of labs across the world to decipher the binding potential of newly identified histone-reading proteins.




  1. Strahl, B. D. & Lombardi, J. (1994). Microdetermination of dry mass content in the uterine fluid of four species of viviparous sharks (Squalus acanthias, Carcharhinus plumbeus, Mustelus canis and Rhizoprionodon terraenovae). Biochem. Physiol. 108A:213-219.


  1. Ghosh, B. R., Wu, J. C., Strahl, B. D., Childs, G. V. & Miller, W. L. (1996). Inhibin and estradiol alter gonadotropes differentially in ovine pituitary cultures: changing gonadotrope numbers and calcium responses to gonadotropin-releasing hormone. Endocrinology 137:5144-5154.
  2. Strahl, B. D., Huang, H.-J., Pederson, N. R., Wu, J. C., Gosh, B. R. & Miller, W.L. (1997). Two proximal AP-1-binding sites are sufficient to stimulate transcription of the ovine follicle-stimulating hormone-ß gene. Endocrinology 138:2621-2631.
  3. Strahl, B. D., Huang, H.-J., Sebastian, J., Ghosh, B. R. & Miller, W. L. (1998). Transcriptional activation of the ovine follicle-stimulating hormone ß-subunit gene by GnRH: involvement of two AP-1-binding sites and protein kinase C. Endocrinology 139:4455-4465.
  4. Huang, H-J., Sebastian J., Strahl, B. D., Wu, J. C. & Miller, W. L. (2001). The promoter for ovine follicle-stimulating hormone-ß gene (FSHß) confers FSHß-like expression on luciferase in transgenic mice: regulatory studies in vivo and in vitro. Endocrinology 142:2260-2266.
  5. Huang, H-J., Sebastian J., Strahl, B. D., Wu, J. C. & Miller, W. L. (2001). Transcriptional Regulation of the ovine FSH-beta gene by activin and GnRH: Involvement of two proximal AP-1 Sites for GnRH-Stimulation. Endocrinology 142:2267-2274.
  6. Miller, W. L., Shafiee-Kermani, F., Strahl B. D., Huang, H. J. (2002) The nature of FSH induction by GnRH. Trends Endocrinol. Metab. 6:257-263.



  1. Strahl, B. D., Ohba, R., Cook, R. G. & Allis, C. D. (1999). Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in Tetrahymena. Natl. Acad. Sci. USA 96:14967-14972.
  2. Strahl, B. D. & Allis, C. D. (2000). The language of covalent histone modifications. Nature 403:41-45.
  3. Rea, S., Eisenhaber, F., O’Carroll, D., Strahl, B. D., Sun, Z-W, Opravil, S., Schmid, M., Mechtler, K., Ponting, C., Allis, C. D. & Jenuwein, T. (2000). Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406:593-599 (Nature article).
  4. Nakayama, J. -I., Rice J. C., Strahl, B. D., Allis, C. D. & Grewal, S. I. S. (2001) Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292:110-113.
  5. Strahl, B. D.*, Briggs, S. D.*, Brame, C. J., Caldwell, J. A. Koh, S., Ma, H., Cook, R. G., Shabanowitz, J., Hunt D. F., Stallcup, M. R. & Allis, C. D. (2001) Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1. Current Bio. 11:996-1000.
  6. Wang, H, Huang, Z. -Q., Xia, l., Feng, Q., Erdjument-Bromage, H., Strahl, B. D., Briggs, S. D. Allis C. D, Wong, J., Tempst, P. & Zhang, Y. (2001) Methylation of histone H4 at arginine 3 facilitates transcriptional activation by nuclear hormone receptor. Science 293:853-857.
  7. Briggs, S. D., Bryk, M. Strahl, B. D., Cheung, W. L. Davie, J. K., Dent, Y. R. S., Winston, F. & Allis, C. D. (2001) Histone H3 lysine 4 methylation is mediated by Set1 and required for rDNA silencing in Saccharomyces cerevisiae. Genes and Dev. 15:3286-3295.
  8. Bryk, M., Briggs, S. D., Strahl B. D., Curcio, M. J., Allis, C. D. & Winston F. (2002) Set1, a factor required for methylation of histone H3, regulates rDNA silencing in Saccaromyces cervisiae by a Sir2-independent mechanism. Current Bio. 12:165-170.
  9. Ma, H., Baumann, C. T., Li, H., Strahl, B.D., Rice, R., Jelinek, M. A., Aswad, D. W., Allis, C. D., Hager, G. L. & Stallcup, M. R. (2001) Hormone-dependent, CARM1-directed, arginine-specific methylation of histone H3 on the mouse mammary tumor virus promoter. Current Bio. 11:1981-1985.
  10. Strahl, B. D., Grant, P. A., Briggs, S. D., Bone J. R., Caldwell, J. A., Cook, R. G., Sun, Z.-W., Mollah, S., Shabanowitz, J., Hunt, D. F. & Allis, C. D. (2002) Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. Cell. Biol. 22:1298-1306.
  11. Li, J., Lin, Q., Yoon, H.-G., Strahl, B. D., Allis, C. D. & Wong, J. (2002) Involvement of histone methylation and phoshporylation in regulation of transcription by thyroid hormone receptor. Cell. Biol. 22:5688-5697.



  1. Briggs, S. B. & Strahl, B. D. (2002) Unraveling heterochromatin. Nature Genet., 30:241-242.
  2. Briggs, S. B., Xiao, T., Sun, Z.-W., Caldwell, J. A., Shabanowitz, J., Hunt, D. F., Allis, C. D. & Strahl, B. D. (2002) Trans-histone regulatory pathway in chromatin. Nature, 418:498.
  3. Xiao, T., Hall, H., Kizer, K. O., Shibata, Y., Hall, M. C., Borchers, C. H. & Strahl, B. D. (2003) Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. Genes & Dev. 17:654-663.
  4. Anest, V., Hanson L., Cogswell P. C., Steinbrecher K. A., Strahl B. D., & Baldwin A. S. (2003) A nucleosomal function for IkB kinase-b in NF-kB-dependent gene expression. Nature, 423:659-663.
  5. Lee, C.-K., Shibata, Y., Rao, B., Strahl, B. D. & Lieb, J. D. (2004) Evidence for Nucleosome Depletion at Active Regulatory Regions Genomewide. Nature Genet., 36:900-905.
  6. Lee, D. Y., Teyssier, C., Strahl, B. D. & Stallcup, M. R. (2005) Role of Protein Methylation in Regulation of Transcription. Endocrine Reviews 26:147-170.
  7. Xiao, T. Kao, C. F., Krogan, N., Sun, Z.-W., Greenblatt, J. F., Osley, M. A., & Strahl, B. D. (2005) Histone H2B ubiquitylation is associated with elongating RNA polymerase II. Mol Cell Biol. 25:637-651.
  8. Kizer, O. K., Phatnani, H. P., Shibata, Y., Hall, H., Greenleaf, A. L. & Strahl, B. D. (2005) A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcription elongation. Mol Cell Biol. 25:3305-3316.
  9. Adhvaryu, K. K., Morris, S., Strahl, B. D. & Selker, E.U. (2005) Methylation of histone H3 lysine 36 is required for normal development in Neurospora crassa. Eukaryot Cell. 4:1455-1464.
  10. Morris, S. A., Shibata, Y., Noma, K.-I., Tsukamoto, Y., Warren, E., Temple, B., Grewal, S. I. S. & Strahl, B. D. (2005) Histone H3 K36 methylation is associated with transcription elongation in Schizosaccharomyces pombe. Eukaryot Cell. 4:1446-1454.
  11. Laribee, R. N., Krogan, J. N., Xiao, T., Shibata, Y., Hughes, T. R., Greenblatt, J. F. & Strahl, B. D. (2005) BUR kinase selectively regulates H3 K4 trimethylation and H2B ubiquitylation through recruitment of the PAF elongation complex. Current Bio. 15:1487-1493.
  12. Rao, B., Shibata, Y., Strahl, B. D. & Lieb, J. D. (2005) Dimethylation of Histone H3 at Lysine 36 Occurs Co-transcriptionally to Demarcate Regulatory and Non-Regulatory Chromatin Genome-wide. Mol Cell Biol. 25:9447-9459.
  13. Keogh, M.-C., Kurdistani, S. K., Morris, S. A., Ahn, S. H., Collins, S. R., Podolny, V., Chin, K., Punna, T., Thompson, N. J., Boone, C., Emili, A., Weissman, J. S., Hughes, T. R., Strahl, B. D., Grunstein, M., Greenblatt, J. F., Buratowski, S., & Krogan, N. J. (2005) Co-transcriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 123:593-605.
  14. Vojnic, E., Simon, B., Strahl, B. D., Sattler, M. & Cramer, P. (2006) Structure and CTD binding of the Set2 SRI domain that couples histone H3 K36 methylation to transcription. J Biol Chem. 281:13-15.
  15. Tripic, T., Edmondson, D., Davie, J, Strahl, B. D. & Dent, S.R. (2006) The Set2 methyltransferase associates with Ssn6 yet Tup1-Ssn6 repression is independent of histone methylation. Biochem Biophys Res Comm. 339:905-14.
  16. Biswas, D., Duttu-Biswas, R., Mitra, D., Shibata, Y., Strahl, B. D., Formosa, T., Stillman, D. J. (2006) Opposing roles for Set2 and yFACT in regulating TBP binding at promoters. EMBO J. 25:4479-4489.
  17. Kizer, O. K., Xiao, T. & Strahl, B. D. (2006) Accelerated nuclei preparation and methods for the analysis of histone modifications in yeast. Methods 40:296-302.
  18. Xiao, T., Shibata, Y., Rao, B., Laribee, R. N., Krogan, J. N., Greenblatt, J. F., Rourke, R. O., Buck, M. J., Lieb, J. D. & Strahl, B. D. (2007) The RNA Pol II kinase Ctk1 regulates positioning of a 5' histone methylation boundary along genes. Mol Cell Biol. 27:721-731.
  19. Garcia, B. A., Hake, S. B., Diaz, R. L., Kauer, M., Morris, S. A., Recht, J., Shabanowitz, J., Mishra, N., Strahl, B. D., Allis, C. D. & Hunt, D. F. (2007) Organismal differences in post-translational modification in histones H3 and H4. J Biol Chem. 282:7641-7655.
  20. Morris, A., Rao, B., Garcia, B. A., Hake, S. B., Diaz, R. L., Shabanowitz, J., Hunt, D. F., Allis, C. D., Lieb, J. D. & Strahl, B. D. (2007) Identification of histone H3 lysine 36 acetylation as a highly conserved modification. J Biol Chem. 282:7632-7640.
  21. Laribee, R. N., Fuchs, S. M. & Strahl B. D. (2007) H2B ubiquitylation in transcriptional control: a FACT finding mission. Genes & Dev. 21:737-743.
  22. Laribee, R. N., Shibata, Y., Mersman, D. P., Roguev, A., Collins, S. R., Kemmeren, P., Weissman, J. S., Briggs, S. D., Krogan, N. J.* & Strahl, B. D.* (2007). The CCR4/NOT complex associates with the proteasome and regulates histone methylation. Proc Natl Acad Sci USA 104:5836-5841.
  23. Wyce, A., Xiao, T., Whelan, K. A., Kosman, C., Walter, W., Eick, D., Hughes, T. R., Krogan, N. J., Strahl, B. D. & Berger, S. L. (2007) H2B ubiquitylation acts as a barrier to Ctk1 nucleosomal recruitment prior to removal by Ubp8 within a SAGA-related complex. Mol Cell. 27:275-88.
  24. Rivenbark, A. G. & Strahl B. D. (2007) Unlocking cell fate. Science 318:403-404.
  25. Merker, J. D., Dominska, M., Greenwell, P. W., Rinella, E., Bouck, D. C., Shibata, Y., Strahl, B. D., Mieczkowski, P. & Petes, T. D. (2008) The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae. DNA Repair 7:1298-308.
  26. Youdell, M. J.*, Kizer, O. K.*, Kisseleva-Romanova, E. Fuchs, S. M., Duro, E., Korn, K., Strahl, D. & Mellor, J. (2008) Spt6 controls methylation of lysine 36 on histone H3 to stabilize transcribed chromatin. Mol Cell Biol. 16:4915-4926.
  27. Henikoff, S., Strahl, B. D. & Warburton P. E. (2008) Epigenomics: a roadmap to chromatin. Science. 322:853.
  28. Fuchs, S. M., Laribee, R. N. & Strahl, B. D. (2009) Protein modifications in transcription elongation. BBA - Gene Regulatory Mechanisms. 1789:26-36.
  29. Lickwar, C.*, Rao, B.*, Shabalin, A., Nobel, A., Strahl, B. D. & Lieb, J. D. (2009) The Set2/Rpd3S pathway suppresses cryptic transcription without regard to gene length or transcription frequency PLoS ONE. 4:e4886
  30. Nakanishi, S., Lee, J. S., Gardner, K. E., Gardner, J. M., Takahashi, Y-H., Chandrasekharan, M. B., Sun, Z-W., Osley, M. A., Strahl, B. D., Jaspersen, S. L. & Shilatifard, A. (2009) Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1. J of Cell Biol. 186:371-377.
  31. Fuchs, S. M., Krajewski, K., Miller, V., Baker, R. W. & Strahl, B. D. (2011) Influence of combinatorial histone modifications on antibody and effector protein recognition. Current Biology. 11:53-58.
  32. Ramachandran, S., Vogel, L., Strahl, B. D.* & Dokholyan, N. V.* (2011) Thermodynamic stability of protein-protein interaction is a necessary but not sufficient driving force for evolutionary conservation. PLoS Comput Biol. 7:e1001042.
  33. Gardner K. E., Zhou, L., Parra, M. A., Chen, X. & Strahl, B. D. (2011) Identification of lysine 37 of histone H2B as a novel site of methylation. PLoS ONE. 6:e16244.
  34. Gardner, K. E., Allis, C. D. & Strahl, B. D. (2011) OPERating ON chromatin, a colorful language where context matters. Mol. Biol. 409:36-46.
  35. Kerr, S. C., Azzouz, N., Fuchs, F. S., Collart, M. A., Strahl, B. D., Corbett, A. H. & Laribee, R. N. (2011) The CCR4-NOT complex physically and functionally interacts with the mRNA export pathway. PLoS ONE. 6:e18302.
  36. Fuchs, S. M. & Strahl, B. D. (2011) Antibody recognition of histone post-translational modifications: emerging issues and future prospects. Epigenomics. 3:247-249.
  37. Fuchs, S. M., Kizer, K. O., Braberg, H., Krogan, N. & Strahl, B. D. (2012) RNA polymerase II CTD phosphorylation regulates protein stability of the Set2 methyltransferase and histone H3 di- and trimethylation at lysine 36. J Biol Chem. 287:3249-3256.
  38. Rivenbark, A. G., Stolzenburg, S., Yuan, X., Strahl, B. D. & Blancafort, P. (2012) Epigenetic reprogramming of cancer cells by targeted DNA methylation. Epigenetics. 7:1-11.
  39. Rothbart, S. B., Lin, S., Britton, L.-M., Krajewski, K., Keogh, M.-C., Garcia, B. & Strahl, B. D. (2012) Poly-acetylated chromatin signatures are preferred epitopes for site-specific histone H4 acetyl antibodies. Scientific Reports. 2:489.
  40. Rothbart, S. B., Krajewski, K., Strahl B. D., Fuchs, S. M. (2012) Peptide microarrays to interrogate the histone code. Methods Enzymol. 512:107-135.
  41. Stolzenburg, S., Rots, M. G., Beltran, A. S., Rivenbark, A. G., Yuan, X., Strahl, B. D. & Blancafort, P. (2012) Targeted silencing of the oncogene transcription factor SOX2 in breast cancer. Nucleic Acid Res. 40:6725-6740.
  42. Bánfai, B., Jia, H., Khatun, J., Wood, E., Risk, B., Gundling, W., Kundaje, A., Gunawardena, H. P., Yu, Y., Xie, L., Krajewski, K., Strahl, B. D., Chen, X., Bickel, P. J., Giddings, M. C., Brown, J. B. & Lipovich, L. (2012) Long non-coding RNAs are rarely translated. Genome Research. 22:1646-1657.
  43. Rothbart, S. B., Krajewski, K., Nady, N., Tempel, W., Xue, S., Badeaux, A. I., Barsyty-Lovejoy, D., Martinez, J. Y., Bedford, M. T., Fuchs, S. M., Arrowsmith, C. H. & Strahl, B. D. (2012) Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Nature Structural & Molecular Biology. 19:1155-1162.
  44. Rizzardi, L. F., Dorn, E. E. Strahl B. D. & Cook J. G. (2012) H3K4 di-methylation promotes DNA replication origin function in Saccharomyces cerevisiae. Genetics 192:371-384.
  45. Nishikori, S., Fuchs, S. M., Yasui, N., Wojcik, J., Koide, A., Strahl, B. D. & Koide, S. A (2012) quantitative and sensitive method for characterizing anti-histone antibodies. Mol. Biol. 424:391-399.
  46. Ali, M., Yan, K., Lalonde, M.-E., Degerny, C., Rothbart, S. B., Strahl, B. D., Cote, J., Yang, X-.J. & Kutateladze, T., G. (2012) Tandem PHD fingers of MORF/MOZ acetyltransferases display selectivity for acetylated histone H3 and are required for the association with chromatin. Mol. Biol. 424:328-288.
  47. Cai, L., Rothbart, S. B., Lu, R., Xu, B., Tripathy, A., Chen, W.-Y., Zheng, D., Patel, D. J., Allis, C. D., Strahl, B. D., Song, J., Wang, G. G. (2013) An H3K36 methylation-engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting. Molecular Cell. 49:571-582.
  48. Law, J. A., Du, J., Hale, C. J., Feng, S., Krajewski, K., Strahl, B. D., Patel, D. J. & Jacobsen, S. E. (2013) SHH1 recruits RNA Polymerase-IV to RNA-directed DNA methylation targets. Nature. 498:385-389.
  49. Rothbart, S. B., Dickson, B. M., Ong, M. S., Krajewski, K., Houliston, S., Kireev, D. B., Arrowsmith, C. H. & Strahl, B. D. (2013) Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation. Genes & Development. 27:1288-1298.
  50. Ali, M., Rincon-Arano, H., Zhao., W., Rothbart, S. B., Tong, Q., Parkhurst, S., Strahl B. D., Deng, L.-W., Groudine, M., Kutateladze, T. G. (2013) Molecular basis for chromatin binding and regulation of MLL5. Proc Natl Acad Sci USA. 110:11296-11301.
  51. Gatchalian, J., Fütterer, A., Rothbart, S. B.,Tong, , Rincon-Arano, H., Sánchez de Diego, A. Groudine, M., Strahl, B. D., Martínez-A, C., van Wely, H. M. K. & Kutateladze, T. G. Dido3 PHD modulates cell differentiation and division. (2013) Cell Reports. 11:148-158.
  52. Kinkelin, K., Wozniak, G. G., Rothbart, S. B., Lidschreiber, M., Strahl B. D. & Cramer, P. Structures of RNA polymerase II complexes with Bye1, a chromatin-binding PHF3/DIDO1 homologue. (2013) Proc Natl Acad Sci USA. 110:15277-15282.
  53. McDaniel S. L. & Strahl, B. D. (2013) Stress-Free with Rpd3: A unique chromatin complex mediates the response to oxidative stress. Mol Cell Biol. 33:3726-3727.
  54. Hattori, T., Taft, J., Swift, K., Luo, H., Witt, H., Slattery, M., Koide, A., Ruthenburg, A. J., Krajewski, K., Strahl, B. D., White, K. P., Farnham, P. J., Zhao, Y., Koide, S. (2013) Recombinant antibodies to histone posttranslational modifications. Nature Methods. 10:992-995.
  55. Dronamraju, R. & Strahl B. D. (2014) A feed forward circuit comprising Spt6, Ctk1 and PAF regulates Pol II CTD phosphorylation and transcription elongation. Nucleic Acids Research. 42(2):870-881.
  56. Klein, B. J., Piao, L., Xi, Yuanxin, Rincon-Arano, H., ROthbart, S. B., Larson, C., Wen, H., Zheng, X., Cortazar, M., Pena, P. V., Mangan, A., Bentley, D. L., Strahl, B. D., Groudine, M., Li, W., Shi, X., Kutateladze, T. G. (2014) The histone-H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD dingers. Cell Reports. 6:1-11.
  57. Kim, H.-S., Mukhopadhyay, R., Rothbart, S. B., Silva, A. C., Vanoosthuyse, V., Radovani, E., Kislinger, T., Roguev, A., Ryan, C. J., Xu, J., Jahari, H., Hardwick, K., G., Greenblatt, J. F., Krogan, N. J., Fillingham, J., S., Strahl, B. D., Bouhassira, E., E., Edelmann, W. & Keogh, M.-C. (2014) Identification of a novel Bromodomain/Casein Kinase II/TAF-containing complex as a regulator of mitotic condensin function. Cell Reports. 6:1-14
  58. Rothbart S. B. & Strahl, B. D. (2014) Interpreting the language of histone and DNA modifications. BBA - Gene Regulatory Mechanisms. 1016/j.bbagrm.2014.03.001
  59. Wozniak, G. G. & Strahl, B. D. (2014) Hitting the 'Mark': Interpreting Lysine Methylation in the Context of Active Transcription. BBA - Gene Regulatory Mechanisms. 1016/j.bbagrm.2014.03.002.
  60. Greer, E. L., Beese-Sims, S. E., Spadafora, R., Rothbart, S. B., Badeaux, A. I., Strahl, B. D., Colaiácovo, M. P. & Shi, Y. A (2014) histone methylation network regulates transgenerational epigenetic memory in elegans. Cell Reports. 7:113-26.
  61. Jha, D. K. & Strahl, B. D. (2014) H3K36 methylation regulates chromatin remodeling and checkpoint activation after DSB. Nature Commun. 5:3965.
  62. Shanle, E. K., Rothbart, S. B. & Strahl, B. D. (2014) Chromatin biochemistry enters the next generation of code ‘seq-ing’ Nature Methods. 11:799-800.
  63. Wozniak, G. G. & Strahl, B. D. (2014) Catalysis-dependent stabilization of Bre1 fine-tunes histone H2B ubiquitylation to regulate gene transcription. Genes and Development. 28:1647-1652.
  64. Jha, D. K. & Strahl, B. D. (2014) SET-ing the stage for DNA repair. Nat Struct Mol Biol. 5:655-657.
  65. Gilbert, T. M.*, McDaniel, S. L.*, Byrum., S. D., Cades, J. A., Dancy, B. C. Y, Wade, H., Tackett, A. J., Strahl, B. D.* & Taverna, S. D.* (2014) A PWWP domain-containing protein targets the NuA3 acetyltransferase complex via H3 lysine 36 trimethylation to coordinate transcriptional elongation at coding regions. Mol Cell Proteomics. 13:2883-2895.
  66. Dumesic, P. A., Homer, C. M., Moresco, J. J., Pack, L. R., Shanle, E. K., Coyle, S. M., Strahl, B. D., Fujimori, D. G., Yates, J. R. & Madhani, H. D. (2015) Product binding enforces the genomic specificity of a yeast polycomb repressive complex. Cell. 160:204-218.
  67. Tong, Q., Cui, G., Botuyan, M. V., Rothbart, S. B., Hayashi, R., Musselman, C. A., Appella, E., Strahl, B. D., Mer, G. & Kutateladze, T. G. (2015) Structural plasticity of methyllysine recognition by the tandem Tudor domain of 53BP1. Structure. 23:312-21.
  68. Tong, Q., Mazur, S., J., Rincon-Arona, H., Rothbart, S. B., Kuznetsov, D. M., Cui, G., Liu, W. H., Gete, Y., Klein, B. J., Jenkins, L., Mer, G., Kutatelasze, A., G., Strahl, B. D., Groudine, M., G., Appella, E. & Kutateladze, T., G. An acetyl-methyl switch drives a conformational change in p53. Structure. 23:322-31.
  69. McKay, D. J., Klusza, S., Penke, T. J., R., Meers, M. P., Curry, K. P., McDaniel, S. L., Malek, P. Y., Cooper, S. W., Tatomer, D., C., Lieb, J. D., Strahl, B. D., Duronio, R. J. & Matera, A. G. (2015) Interrogating the function of metazoan histones using engineered gene clusters. Developmental Cell. 32:373-86.
  70. Perfetti, M. T., Baughman, B. M., Dickson, B. D. Mu, Y., Cui, G., Mader, P., Dong, A., Norris, J. L., Rothbart, S. B., Strahl, B. D., Brown, P. J., Janzen, W. P., Arrowsmith, C. H., Mer, G., McBride, K., James, L., & Frye, S. V. (2015) Identification of a Fragment-like Small Molecule Ligand for the Methyl-lysine Binding Protein, 53BP1. ACS Chemical Biology. 10:1072-1081.
  71. Rothbart, S. B., Dickson, B. M. & Strahl, B. D. (2015) From Histones to Ribosomes: A Chromatin Regulator Tangoes with Translation. Cancer Discovery. 5:228-30.
  72. Wang, L., Xie, L., Ramachandran, S., Lee, Y., Yan, Z., Zhou, L., Krajewski, K., Liu, F., Zhu, C., Chen, D., Strahl, B. D., Jin, J., Dokholyan, N. V. & Chen, X. (2015) Non-canonical bromodomain within DNA-PKcs promotes DNA damage response and radioresistance through recognizing an IR-induced acetyl-lysine on H2AX. Chemistry & Biology. 22:1-13.
  73. Rothbart, S. B., Dickson, B. M., Raab, J. R., Grzybowski, A. T., Krajewski, K., Guo, A. H., Shanle, E. K., Josefowicz, S. Z., Fuchs, S. M., Allis, C. D., Magnuson, T. R., Ruthenburg, A. J. & Strahl, B. D. (2015) An interactive database for the assessment of histone antibody specificity. Molecular Cell. 59:502-511.
  74. Ali, F. A., Daze, K. D., Rothbart, S. B., Strongin, D. E., Rincon-Arano, H., Allen, H. F., Li, J., Groudine, M., Strahl, B. D., Hof, F. & Kutateladze, T. G. (2015) Molecular Insights into Inhibition of the Methylated Histone-Plant Homeodomain Complexes by Calixarenes. Journal of Biological Chemistry. 290:22919-22930.
  75. Zhang, Z.-M., Rothbart, S. B., Allison, D., Cai, Q., Harrison, J. S., Li, L., Wang, Y., Strahl B. D., Wang, G. G., Song, J. (2015) An allosteric interaction links USP7 to deubiquitination and chromatin targeting of UHRF1. Cell Reports. 12:1400-1406.
  76. Simon, J. M., Parker, J. S., Liu, F., Rothbart, S. B., Ait-Si-Ali, S., Strahl, B. D., Jin, j., Davis, I. J., Mosley, A. L. & Pattenden, P. G. (2015) A role for Widely Interspaced Zinc finger (WIZ) in retention of the G9a methyltransferase on chromatin. Journal of Biological Chemistry. 290:26088-26102.
  77. Shanle, E. K, Andrews, F. H., Meriesh, H., McDaniel, S. L., Dronamraiu, R., DiFiore J., Jha, D., Wozniak, G. G., Bridgers, J., Kerschner, J. L., Martín, G. M., Morrison A. J., Krajewski, K., Kutateladze, T.* & Strahl, B. D.* (2015) Association of Taf14 with acetylated histone H3 directs gene transcription and the DNA damage response. Genes & Development. 29:1789-1794.
  78. Chen, S., Ze, Y., Wilkinson, A., Deshpande, A. J., Krajewski, K., Strahl, B. D., Armstrong, S. A., Patel, D., J. & Gozani, O. (2105) The PZP domain of AF10 senses unmodified H3K27 to regulate DOT1L-mediated methylation of H3K79. Molecular Cell. 60:319-327.
  79. Shanle, E. K., Tsun, I. K. & Strahl, B. D. (2015) A course-based undergraduate research experience investigating p300 bromodomain mutations. Biochemistry and Molecular Biology Education. doi: 10.1002/bmb.20927.
  80. Cliffe, A. R., Vogel, J. L., Arbuckle, J. H., Geden, M. J., Rothbart, S. B., Cusack, C. L., Strahl, B. D., Kristie, T. M., Deshmukh, M. A (2015) Neuronal stress pathway mediating a histone Methyl/Phospho switch is required for Herpes Simplex Virus Reactivation. Cell Host and Microbe. 18:649-658.
  81. Andrews, F. H.*, Gatchalian, J., Krajewski, K., Strahl, B. D. & Kutateladze, T. G. Regulation of methyllysine readers through phosphorylation. ACS Chemical Biology. DOI: 10.1021/acschembio.5b00802.
  82. Andrews, F. H.*, Shanle, E. K.*, Strahl, B. D.* & Kutateladze, T. G.* Acetyllysine binding activity of the YEATS domains is essential for transcription. Transcription (In Press).
  83. Hattori, T., Lai, D., Dementieva, I. S., Montano, S. P., Zheng, Y., Akin, L., Swift, K., M., Grzybowski, A. T., Koide, A., Krajewski, K., Strahl, B. D., Kelleher, N. L., Ruthenburg, A. J. & Koide, S. Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation. Proc Natl Acad Sci USA (In Press).

Lab Opportunities - Postdoctoral positions to study the histone code and gene regulation

The Strahl lab provides a unique opportunity for inquisitive researchers to study the role of histone post-translational modifications (e.g. acetylation, methylation and ubiquitylation) in chromatin structure and function. We are employing a variety of different approaches (biochemical, genetic and proteomic) to address how these post-translational modifications contribute to gene transcription/DNA repair and how they work in combination to regulate a possible histone code (see Strahl and Allis, Nature403:41-45, 2000 and Garnder, Allis, and Strahl, J of Mol Bio 409:36-46). Recent studies show that multiple and adjacent domains in chromatin-associated proteins work in combination to "readout “specific histone modification signatures to regulate fundamental biological processes such as DNA methylation (e.g., see Rothbart...Strahl, 2013 Genes & Development, 27:1288-98). Yet, the extent to which other histone-associated proteins function in this manner is poorly understood, and as such, is a significant area we are currently exploring.

We are continually seeking enthusiastic and highly motivated individuals with a strong publication background to join us in this very exciting field of study. A Ph.D. with molecular biology experience is required for the postdoctoral position. Additional experience in proteomics, microarray and/or yeast manipulation is preferred but not necessary as we seek individuals with high training potential.

It is important to mention that UNC offers an outstanding environment to carry out studies in the Strahl lab. There are a wide number of core facilities, expert epigenetic faculty to consult and collaborate with, and an extremely friendly living environment here in Chapel Hill. In addition, UNC harbors two outstanding postdoctoral training programs for which you can gain independent funding. One is the UNC Lineberger Cancer Center Postdoctoral Training Program, and the other the SPIRE training program (which is centered more so on teaching development). I strong encourage all of my trainee's to apply for these incredible training programs when joining the lab, which offer great training and career development opportunities. In all, UNC and my lab offer an outstanding place to train for a scientific career in the biomedical sciences.

If you are interested in pursuing research with our lab, please remit your CV, along with the names of 2-3 references, to Dr. Brian Strahl @





Chromatin and Epigenetics