Last Updated: 11/17/2008

Research Interests
DNA is faithfully packaged within the nuclei of our cells through the actions of histone proteins. These proteins create individual histone-DNA complexes referred to as nucleosomes, which are further folded into higher-order chromatin structures that are poorly defined. To a large extent, chromatin structure and function is dictated by histone post-translational modifications, which include acetylation, methylation, ubiquitylation and phosphorylation. Studies indicate that these modifications work together in the form of a ‘histone code’ to regulate the recruitment of effector proteins that then alter the structure and function of chromatin.

Although chromatin has been studied intensely for over thirty years, we still know very little regarding how distinct chromosomal domains such as “euchromatin” and “heterochromatin” become established and maintained, and how the underlying DNA within this highly compact and repressive environment is made accessible to the protein machineries that utilize it. Our lab is addressing these issues by examining the process of RNA polymerase II transcription. We seek to understand how gene transcription occurs at the “right place” and at the “right time” in the genome, and the mechanisms by which histones, histone variants, and histone post-translational modifications contribute to this event. Recently, our lab and others have identified roles for several histone-modifying enzymes during the transcription process. These enzymes associate with the polymerase during transcript elongation and alter the chromatin environment to make it more or less permissive for transcriptional initiation and elongation events. As an example, co-transcriptional methylation of histone H3 at lysine 36 by Set2 results in the recruitment of a histone deacetylase complex that keeps the coding region of genes in a more repressed state that is resistant to inappropriate transcriptional initiation. Current efforts are aimed at understanding how this and other histone-modifying enzymes contribute to chromatin organization, nucleosome stability and gene regulation.

Recent Accomplishments and Honors
2008 Recipient of an Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) award

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

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

2004 Pew Scholar in the Biomedical Sciences

2003 Recipient of a Presidential Early Career Award (PECASE)

Training
Ph.D., North Carolina State University

Postdoctoral work at University of Virginia with Dr. C. David Allis

Publications
Fuchs, S. M., Laribee, R. N. & Strahl, B. D. Protein modifications in transcription elongation. BBA - Gene Regulatory Mechanisms (in press).

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.

Rivenbark, A. G. & Strahl B. D. (2007) Unlocking cell fate. Science 318:403-404.

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.

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.

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 Biology (in press).

Kizer, O. K., Phatnani, H. P., 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.

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 and Dev. 17:654-663.

Anest, V., Hanson J. L., Cogswell P. C., Steinbrecher K. A. , Strahl B. D., & Baldwin A. S. (2003) A nucleosomal function for IkB kinase-alpha in NF-kB-dependent gene expression. Nature, 423:659-663.

Briggs, S. B., Xiao, T., Sun, Z.-W., Caldwell, J. A., Shabanowitz, J., Hunt, D. F., Allis, C. D. & Strahl, B. D. (2002) Gene silencing: trans-histone regulatory pathway in chromatin. Nature, 418:498.

Strahl, B. D. & Allis, C. D. (2000). The language of covalent histone modifications. Nature 403:41-45.

E-mail: brian_strahl@med.unc.edu
Telephone: 919-843-3896
FAX: 919-966-2852
Address: 3060 Genetic Medicine Chapel Hill, NC 27599
URL: www.med.unc.edu/~bstrahl

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