Professor and Vice Chair
Biochemistry & Biophysics
Cancer Cell Biology
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.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
- 2019 Recipient of UNC’s Excellence in Basic Science Mentoring Award
- 2018 Recipient of UNC’s Excellence in Basic Science Mentoring Award
- 2018 Names an Oliver Smithies Investigator, UNC
- 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 (2017 & 2018)
Dranamraju, R., Kerschner, J. L., Peck, S. A., Patel, D., Aslam, S., Mosley, A. L. & Strahl, B. D. (2018) Casein Kinase II Phosphorylation of Spt6 Enforces Transcriptional Fidelity by Maintaining Spn1-Spt6 Interaction. In Press at Cell Reports.
Lerner, A. M., Yumerefendi, H., Goudy, O. J., Strahl, B. D. & Kuhlman K. (2018) Engineering improved photoswitches for the control of nucleocytoplasmic distribution. ACS Synthetic Biology.0.1021/acssynbio.8b00368.
Klein, B.J.,Vann, K. R., Andrews, F. H., Wang, W. W, Zhang, J., Zhang, Y., Beloglazkina, A. A., Mi, W., Li, Yuanyuan, Li., H., Shi, X., Kutateladze, A. G., Strahl, B. D., Liu, W. R. & Kutateladze, T. G. (2018) Structural insights into the π-π-π stacking mechanism and DNA-binding activity of the YEATS domain. Nature Commun. 9:4574.
Klein, B.J., Krajewski, K., Restrepo, S., Lewis, P. W.*, Strahl, B. D.* & Kutateladze, T. G.* (2018) Recognition of cancer mutations in histone H3K36 by epigenetic writers and readers. Epigenetics. doi: 10.1080/15592294.2018.1503491.
Slaughter, M. J., Shanle, E. K., McFadden, A. W., Suttle, L. E., Strahl, B. D. & Davis, I. J. (2018) Polybromo-1 (PBRM1) bromodomains variably influence nucleosome interactions and cellular function. J Biol Chem. doi: 10.1074/jbc.RA118.003381.
Dronamraju, R., Hepperla, A. J., Shibata, Y., Adams, A. T., Magnuson, T., Davis, I. J. & Strahl, B. D.(2018) Spt6 association with RNA Polymerase II directs mRNA turnover during transcription. Molecular Cell. 70:1054-1066
Chiang, Y. C., Park, I. Y., Terzo, E. A., Tripathi, D. N., Mason, F. M., Fahey, C. C., Karki, M., Shuster, C. B., Sohn, B., H., Chowdhary, P., Powell, R. T., Ohi, R., Tsai, Y. S., de Cubas, A. A., Khan, A., Davis, I. J., Strahl, B. D., Parker, J. S., Dere, R., Walker, C. L. & Rathmell, W. K. (2018) SET2 haploinsufficiency for microtubule methylation is an early driver of genomic instability in renal cell carcinoma. Cancer Research. 78:3135-3146.
Suh, J. L., Watts, B., Stuckey, J. I., Norris-Drouin, J. L., Cholensky, S. H., Dickson, B. M., An, Y., Mathea, S., Knapp, S., Khan, A., Adams, A. T., Strahl, B. D., Sagum, C., Bedford, M. T., James, L. I., Kireev, D. B. & Frye, S. V. (2018) Quantitative characterization of bivalent probes for a dual bromodomain protein, Transcription Initiation Factor TFIID subunit 1. Biochemistry. 57:2140-2149.
Meers, M. P., Aldemna, K., Duronio, R. J., Strahl, B. D., McKay, D. J. & Matera, A. G. (2018) Transcription start site profiling uncovers divergent transcription and enhancer-associated RNAs in Drosophila melanogaster. BMC Genomics. 19:157.
Dronamraju, R., Jha, D., Eser, E., Dominguez, D., Adams, A., Choudhury, R., Chiang, Y. C., Rathmell, W. K., Emanuele, M. J., Churchman, L. S. & Strahl, B. D. (2018) Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity. Nucleic Acids Research. 46:1331-1334.
Klein, B. J., Ahmad, S., Vann, K. R., Andrews, F. H., Mayo, Z. A., Bourriquen, G., Bridgers, J. B., Zhang, J., Strahl, B. D., Cote, J. & Kutateladze, T. G. (2018) Yaf9 subunit of the NuA4 and SWR1 complexes targets histone H3K27ac through its YEATS domain. Nucleic Acids Research. 46:421-430.
Penke, T., McKay, D. J., Strahl, B. D., Matera, A. G. & Duronio, R. J. (2018) Functional redundancy of variant and canonical histone H3 lysine 9 modification in Drosophila. Genetics. 208:229-244.
Veland, N., Zhong, Y., Gayatri, S., Dan, J, Strahl, B. D., Rothbart, S. B., Bedford, M. T. & Chen T. The arginine methyltransferase PRMT6 regulates DNA methylation and contributes to global DNA hypomethylation in cancer. Cell Reports. 21:3390-3397.
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.