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; CB# 7260
120 Mason Farm Rd.

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 (2016 & 2017)

Tencer, A. H., Cox, K. L., Di, L., Bridgers, J. B., Lyu, J., Wang, X., Sims, J. K., Weaver, T. M., Allen, H. F., Zhang, Y., Gatchalian, J., Darcy, M. A., Gibson, M. D., Ikebe, J., Li, W., Wade, P. A., Hayes, J. J., Strahl, B. D., Kono, H., Poirier, M. G., Musselman, C. A. & Kutateladze, T. G. (2017) Covalent modification of histone H3K9 promotes binding of CHD3. Cell Reports. 21:455-466.

 

Dronamraju, R.*, Ramachandran, S.*, Jha, D. K.*, Adams, A. T., DiFiore, J. V., Parra, M. A., Dokholyan, N. V.* & Strahl, B. D.* (2017) Redundant functions for Nap1 and Chz1 in H2A.Z deposition. Scientific Reports. 7:10791. 

 

Tencer, A. H., Gatchalian, J., Klein, B. J., Khan, A., Zhang, Y., van Wely, K. H. M., Strahl, B. D. & Kutateladze, T. G. (2017) A unique pH-dependent recognition of methylated histone H3K4 by PPS and DIDO3. Structure. 25:1530-1539.

 

McDaniel, S. L., Hepperla, A., Huang, Jie, Kulkarni, V. G., Davis, I. J. & Strahl, B. D. (2017) H3K36 Methylation Regulates Nutrient Stress Response in Saccharomyces cerevisiae by Enforcing Transcriptional Fidelity.  Cell Reports. 19:2371-2382

 

McDaniel, S. L. & Strahl, B. D. (2017) Shaping the Cellular Landscape with Set2/SETD2 methylation. Cellular & Molecular Life Sciences. doi: 10.1007/s00018-017-2517-x. 

 

Khan, A., Bridgers, J. S. & Strahl, B. D. (2017) Expanding the reader landscape of histone acylation. Structure. 25:571-573.

 

Meers, M., P., Henriques, T., Lavender, C. A., McKay, D. J., Strahl, B. D., Duronio, R. J., Adelman, K. & Matera, A. G. (2017) Histone replacement decouples H4 acetylation from cryptic transcription in H3K6 mutants and reveals a post-transcriptional mechanism for maintaining transcriptome fidelity in animals. ELife. pii: e23249. doi: 10.7554/eLife.23249. 

 

Shanle, E. K.*, Shinsky, A. A.*, Bridgers, J. B., Bae, N., Sagum, C., Krajewski, K., Rothbart, S. B., Bedford, M. T.* & Strahl, B. D.* (2017) Histone peptide microarray screen of chromo and Tudor domains defines new histone lysine methylation interactions. Epigenetics & Chromatin. 10:12 doi: 10.1186/s13072-017-0117-5.

 

Savitsky, P., Krojer, T., Fujisawa, T., Lambert, J.P., Picaud, S., Wang, C.Y., Shnale, E. K., Krajewski, K., Friedrichsen, H., Kanapin, A., Goding, C., Schapira, M., Samsonova, A., Strahl, B. D., Gingras, A.C. & Filippakopoulos, P. (2016) Multivalent histone and DNA engagement by a PHD/BRD/PWWP triple reader cassette recruits ZMYND8 to K14ac-rich chromatin.  Cell Reports. 17:2724-2737.

 

Strikoudis, A., Lazaris, C., Trimarchi, T., Galvao Neto, A. L., Yang, Y., Ntziachristos, P., Rothbart, S. D., Buckley, S., Dolgalev, I., Stadtfeld, M., Strahl, B. D., Dynlacht, B. D., Tsirigos, A & Aifantis, I. Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a. Nature Cell Biology. doi: 10.1038/ncb3424.

 

Charpentier, T. H., Waldo, G. L., Lowery-Gionta, E. G., Krajewski, K., Strahl, B. D., Kash, T. L., Harden, K. & Sondek, J. Potent and selective peptide-based inhibition of Gαq. Journal of Biological Chemistry. pii: jbc.M116.740407. 

 

Andrews, F. H., Tong, Q., Sullivan, K. D., Cornett, E., Zhang, Y., Muzaffar, A., Ahn, J., Strahl, B. D., Costello, J. C., Espinosa, J. M., Rothbart, S., B. & Kutateladze, T. G. (2016) Multivalent chromatin engagement and inter-domain crosstalk regulate MORC3 ATPase.  Cell Reports. 16:3195-31207.

 

Harrison, J. S., Cornett, E. M., Goldfarb, D., DaRosa, P. A., Li, Z. M., Yan, F., Dickson, B. M., Guo, A. H., Cantu, D. V., Kaustov, L., Brown, P. J., Arrowsmith, C. H., Klevit, R. E., Erie, D. A., Major, M. B., Krajewski, K., Kuhlman, B., Strahl, B. D. & Rothbart, S. B. (2016) Hemi-methylated DNA regulates DNA methylation inheritance through allosteric control of H3 ubiquitylation by UHRF1. ELife. http://dx.doi.org/10.7554/eLife.17101.001

 

Penke, T. J. R., McKay, D. J., Strahl, B. D., Matera, A. G & Duronio, R. J. (2016) Direct interrogation of the role of H3K9 in metazoan heterochromatin function. Genes & Development. 30:1866-1880.

 

Chen, H., Workman, J. J., Strahl, B. D. & Laribee, R. N. (2016) Histone H3 and TORC1 Prevent Organelle Dysfunction and Cell Death by Promoting Nuclear Retention of HMGB Proteins. Epigenetics & Chromatin. 9:34

  

Hacker, K. E.*, Fahey, C. C.*, Shinsky, S. A.*, Chiang, Y.-C. J.*, DiFiore, J. V.*, Jha, D. K., Vo, A. H., Shavit, J. A. Davis, I, J., Strahl, B. D.* & Rathmell, W. K.* (2016) Structure/Function Analysis of Recurrent Mutations in SETD2 Reveals a Critical and Conserved Role for a SET Domain Residue in Maintaining Protein Stability and H3K36 Trimethylation. Journal of Biological Chemistry. Aug 15. pii: jbc.M116.739375. 

 

Andrews, F. H., Strahl, B. D. & Kutateladze, T. G. (2016) Insights into newly discovered marks and readers of epigenetic information. Nature Chemical Biology. 12:662-668.

 

Cornett, E. M., Dickson, B. M., Vaughan, R. M., Trievel, R. C., Strahl, B. D. & Rothbart, S. B. (2016) Substrate specificity profiling of histone-modifying enzymes by peptide microarray. Methods in Enzymology. 574:31-52. 

 

McDaniel, S. L., Fligor, J. E., Chun, R., Cui, H., Bridgers, J. B., DiFiore, J. V., Guo, A. H., Li, B. & Strahl, B. D. (2016) Combinatorial Histone Readout by the Dual Plant Homeodomain (PHD) Fingers of Rco1 Mediates Rpd3S Chromatin Recruitment and the Maintenance of Transcriptional Fidelity. Journal of Biological Chemistry. 291:14796-14802.

 

Bedard, L. G., Dronamraju, R., Kerschner, J.L., Hunter, G.O., Axley, E.D., Boyd, A.K., Strahl, B.D. & Mosley, A.L. (2016) Quantitative analysis of dynamic protein interactions during transcription reveals a role for casein kinase II in PAF complex phosphorylation and regulation of H2B monoubiquitylation. Journal of Biological Chemistry. 291:13410-13420.

 

Yumerefendi, H., Lerner, A. M., Zimmerman, S. P., Hahn, K., Bear, J. E., Strahl, B. D. & Kuhlman, B. (2016) Light-induced nuclear export reveals rapid dynamics of epigenetic marks. Nature Chemical Biology. 12:399-401.

 

Andrews, F. H.*, Shinsky, A. S.*, Shanle, E. K., Bridgers, J. B., Gest, A., Tsun, I. K., Krajewski, K., Shi, X., Strahl, B. D.* & Kutateladze, T. G.* (2016) The Taf14 YEATS domain is a reader of histone crotonylation. Nature Chemical Biology12:396-398.

 

Gatchalian, J., Mora, C., Shinsky, S. A., Ospina, R. R., Mansilla, A. L., Klein, B. J., Andrews, F. H., Strahl, B. D., van Wely, K. H. M. & Kutateladze, T. G. (2016) Chromatin condensation and recruitment of PHD fingers to histone H3K4me3 are mutually exclusive. Nucleic Acids Research. Mar 25. pii: gkw193. 

 

Sorenson, M. R., Jha, D. K., Ucles, S., Flood, D., Strahl, B. D., Stevens, S. W. & Kress, T. L. (2016) Histone H3K36 methylation regulates pre-mRNA splicing in Saccharomyces cerevisiae. RNA Biology. 13:412-426.

 

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. (2016) Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation. Proc Natl Acad Sci USA.113:2092-2097.

 

Andrews, F. H.*, Shanle, E. K.*, Strahl, B. D.* & Kutateladze, T. G.* (2016) The essential role of acetyllysine binding by the YEATS domain in transcriptional regulation. Transcription. 7:14-20.

 

Andrews, F. H., Gatchalian, J., Krajewski, K., Strahl, B. D. & Kutateladze, T. G. (2016) Regulation of methyllysine readers through phosphorylation. ACS Chemical Biology. 7:14-20.

 

Shanle, E. K., Tsun, I. K. & Strahl, B. D. (2016) A course-based undergraduate research experience investigating p300 bromodomain mutations. Biochemistry and Molecular Biology Education. 44:68-74.

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