Brian Strahl, PhD

Keywords: Chromatin, Epigenetics, Histones, Post-Translational Modifications, Gene Expression, Peptide/Protein Arrays, Protein-Protein interactions

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

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.

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.

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.

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 INFO

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

    Office: 919-843-3896
    Lab: 919-843-3935

    brian_strahl@med.unc.edu

    Lab Location: 3048G Genetic Medicine

    Strahl Lab Website