Brian D Strahl

PhD, Biochemistry & Biophysics, UNC-Chapel Hill, Cancer Cell Biology

Brian D Strahl

PhD
Biochemistry & Biophysics
UNC-Chapel Hill
Cancer Cell Biology

3060 Genetic Medicine Bld
3060 Genetic Medicine; CB# 7260
Chapel Hill, NC 27599
919-843-3896

Brian Strahl - UNC Departmental website
CV or Biosketch

Area of interest

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 still 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, 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 need to utilize it.  The Strahl lab is addressing these issues by examining the process of RNA polymerase II transcription. We aim 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, the Strahl 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 and histone exchange. Current efforts are aimed at understanding how this and other histone-modifying enzymes contribute to chromatin organization, nucleosome stability and gene regulation.

Finally, Brian Strahl's group 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.  These exciting projects are helping to bring new insight into how histones, and the modifications they contain, drive fundamentally important biological processes such as gene transcription and DNA repair in cells, and how their mis-regulation leads to human diseases such as cancer.

Awards and Honors

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

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

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

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)

Recent Publications (2014 & 2015)

  1. 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.
  2. 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.
  3. 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
  4. Rothbart S. B. & Strahl, B. D. (2014) Interpreting the language of histone and DNA modifications. BBA - Gene Regulatory Mechanisms. 10.1016/j.bbagrm.2014.03.001
  5. Wozniak, G. G. & Strahl, B. D. (2014) Hitting the 'Mark': Interpreting Lysine Methylation in the Context of Active Transcription. BBA - Gene Regulatory Mechanisms. 10.1016/j.bbagrm.2014.03.002.
  6. 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 C. elegans. Cell Reports. 7:113-26.
  7. Jha, D. K. & Strahl, B. D. (2014) H3K36 methylation regulates chromatin remodeling and checkpoint activation after DSB. Nature Commun. 5:3965.
  8. 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.
  9. 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.
  10. Jha, D. K. & Strahl, B. D. (2014) SET-ing the stage for DNA repair. Nat Struct Mol Biol. 5:655-657.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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-Induced Histone Methyl/Phospho Switch Mediates HSV Reactivation. Cell Host and Microbe (In Press)
  27. 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).

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