Brian Strahl, PhD

Professor & Dir. of Graduate Studies of Biochemistry & Biophysics

Faculty Director  UNC High-throughput Peptide Synthesis and Array Facility
PHD - NC State University

HONORS & AWARDS

  • Phillip & Ruth Hettleman Prize - 2009
  • NIH Eureka Award - 2008
  • Schering-Plough Research Institute Award - 2004
  • Presidential Early Career Award for Scientists and Engineers - 2003
  • Pew Scholar - 2003

RESEARCH

Histone Modifications and Gene Regulation:

Eukaryotic genomes are highly condensed through their interaction with histone proteins. Such compaction results in the restricted access of proteins to the DNA template.Strahl graphic Thus, a significant question to ask is how chromatin environments are established and maintained, as well as made permissive to the protein machineries that drive transcription, replication, recombination, and repair. One mechanism known to regulate chromatin structure and function are histone post-translational modifications. A wide number of modifications, such as acetylation and methylation, decorate the histone proteins and studies indicate that they work together in the form of a ‘histone code’ to regulate chromatin-based activities.

In our laboratory, we have been exploring the role of histone-modifying enzymes in RNA polymerase II (RNAPII) transcription. Our lab has contributed to the finding that a variety of enzymes that either methylate, acetylate or ubiquitylate histones, contribute to transcription elongation and are associated with the elongating form of RNAPII.  Current efforts are aimed at understanding how these enzymes (and their modifications) contribute to chromatin organization, gene regulation and how their dysregulation leads to cancer.  In addition to our studies into gene regulation, our lab is also engaged in a high-throughput proteomics project involving histone peptide arrays to decipher how histone modifications, and the histone codes they generate, regulate the recruitment of chromatin-associated proteins that govern the diverse functions associated with DNA.

Core Techniques: www.med.unc.edu/biochem/unc-peptides

  • Yeast genetics
  • Protein Purification
  • Peptide Synthesis
  • Peptide Arrays

RECENT PUBLICATIONS  pubmed.png (click for Full Publication List)

  • 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.
  • Jha, D. K. & Strahl, B. D. (2014) H3K36 methylation regulates chromatin remodeling and checkpoint activation after DSB. Nature Commun. 5:3965.
  • 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.
  • 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.
  • 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. An H3K36 methylation-engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting. Molecular Cell. 2013, 49:571-582.
  • Law, J. A., Du, J., Hale, C. J., Feng, S., Krajewski, K., Strahl, B. D., Patel, D. J. & Jacobsen, S. E. SHH1 recruits RNA Polymerase-IV to RNA-directed DNA methylation targets. Nature. 2013, 10.1038/nature12178
  • Fuchs, S. M., Kizer, K. O., Braberg, H., Krogan, N. & Strahl, B. D. RNA polymerase II CTD phosphorylation regulates protein stability of the Set2 methyltransferase and histone H3 di- and trimethylation at lysine 36. J Biol Chem. 2012, 287:3249-3256.
  • Rivenbark, A. G., Stolzenburg, S., Yuan, X., Strahl, B. D. & Blancafort, P. Epigenetic reprogramming of cancer cells by targeted DNA methylation. Epigenetics. 2012, 7:1-11. Rothbart, S. B., Lin, S., Britton, L.-M., Krajewski, K., Keogh, M.-C., Garcia, B. & Strahl, B. D. Poly-acetylated chromatin signatures are preferred epitopes for site-specific histone H4 acetyl antibodies. Scientific Reports. 2012, 2:489.
  • Rothbart, S. B., Krajewski, K., Strahl B. D., Fuchs, S. M. Peptide microarrays to interrogate the histone code. Methods Enzymol. 2012, 512:107-135. Stolzenburg, S., Rots, M. G., Beltran, A. S., Rivenbark, A. G., Yuan, X., Strahl, B. D. & Blancafort, P. Targeted silencing of the oncogene transcription factor SOX2 in breast cancer. Nucleic Acid Res. 2012, 40:6725-6740.
  • 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. Long non-coding RNAs are rarely translated. Genome Research. 2012, 22:1646-1657.
  • 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. Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Nature Structural & Molecular Biology. 2012, 19:1155-1162.
  • Rizzardi, L. F., Dorn, E. E. Strahl B. D. & Cook J. G. H3K4 di-methylation promotes DNA replication origin function in Saccharomyces cerevisiae. Genetics 2012, 192:371-384. Nishikori, S., Fuchs, S. M., Yasui, N., Wojcik, J., Koide, A., Strahl, B. D. & Koide, S. A quantitative and sensitive method for characterizing anti-histone antibodies. J. Mol. Biol. 2012, 424:391-399.
  • Ali, M., Yan, K., Lalonde, M.-E., Degerny, C., Rothbart, S. B., Strahl, B. D., Cote, J., Yang, X-.J. & Kutateladze, T., G. Tandem PHD fingers of MORF/MOZ acetyltransferases display selectivity for acetylated histone H3 and are required for the association with chromatin. J. Mol. Biol. 2012, 424:328-288.
  • Rothbart SB, Krajewski K, Nady N, Tempel W, Xue S, Badeaux AI, Barsyte-Lovejoy D, Martinez JY, Bedford MT, Fuchs SM, Arrowsmith CH, Strahl BD. (2012) Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Nat Struct Mol Biol. Epub ahead of print.
  • 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.
  • 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.  In press at Nucleic Acid Research.
  • 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.
  • 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.
  • Fuchs, S. M. & Strahl, B. D. (2011) Antibody recognition of histone post-translational modifications: emerging issues and future prospects. Epigenomics. 3:247-249.
  • 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.
  • Gardner, K. E., Allis, C. D. & Strahl, B. D. (2011) OPERating ON chromatin, a colorful language where context matters. J. Mol. Biol. 409:36-46.
  • 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.
  • 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.
  • 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
  • Fuchs, S. M., Laribee, R. N. & Strahl, B. D. (2009) Protein modifications in transcription elongation. BBA - Gene Regulatory Mechanisms. 1789:26-36.
  • Youdell, M. J.*, Kizer, O. K.*, Kisseleva-Romanova, E. Fuchs, S. M., Duro, E., Korn, K., Strahl, B. D. & Mellor, J. (2008) Spt6 controls methylation of lysine 36 on histone H3 to stabilize transcribed chromatin. Mol Cell Biol. 16:4915-4926.
  • 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.
  • Morris, S. 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.
  • 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.

      CONTACT INFORMATION

      Strahl Lab Website

      120 Mason Farm Rd,
      Campus Box # 7260
      3060 Genetic Medicine
      Chapel Hill, NC 27599

      Office: 919-843-3896
      Fax (919) 966-2852
      brian_strahl@med.unc.edu

      Lab Rooms: 3048G Genetic Med
      Lab: 919-843-3935