Brian Strahl

Research: Histone modifications and epigenetics; Core Techniques: yeast genetics, peptide synthesis, peptide arrays, mammalian cell culture

 

Oliver Smithies investigator, Professor and Vice-Chair
Faculty Director, UNC High-throughput Peptide Synthesis and Array Facility
Co-Director of Chromatin and Epigenetics Program
(PhD – NC State University)

ACCEPTING STUDENTS

Trained Faculty Mentor endorsed by Office of Graduate Ed UNC Chapel Hill

HONORS & AWARDS

  • UNC Oliver Smithies Investigator: 2018
  • NIH Maximizing Investigators’ Research Award (MIRA), National Institute of General Medical Sciences: 2018
  • Philip & 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 SUMMARY

Eukaryotic genomes are packaged into the nuclei of cells through the actions of histone proteins. These proteins not only play a role in condensing the genome but are fundamental to establishing and maintaining chromatin domains such as euchromatin and heterochromatin. Our lab is addressing how chromatin organization achieved and what factors make the underlying DNA permissive to the protein machineries that drive transcription, replication, recombination, and repair. A large body of work shows that histone post-translational modifications are central to the regulation of chromatin structure and function. These modifications, which include acetylation and methylation, decorate histones and function, at least in part, by recruiting chromatin regulatory proteins to the sites of these modifications. Current efforts are aimed at understanding how histone modifications are installed and removed, and how they are interpreted to regulate genome function.

SELECTED PUBLICATIONS

  • Zhang, Y., Jang, Y., Lee, J.-E., Ahn, J., Xu, L., Holden, M. R., Cornett, E. M., Krajewski, K., Klein, B. J., Wang, S.-P., Dou, Y., Roeder, R. G., Strahl, B. D., Rothbart, S. B., Shi, X., Ge, K. & Kutateladze, T. G. Selective binding of the PHD6 finger of MLL4 to histone H4K16ac links MLL4 and MOF.  In Press at Nature Commun.

  • Petell, C. J., Pham, A. T., Skela, J. & Strahl, B. D. Improved methods for the detection of histone interactions with peptide microarrays.  Sci Rep. 9:6265.

  • Noubouossie D. F., Reeves, B. N., Strahl, B. D. & Key, N. S. (2019) Neutrophils: back in the thrombosis spotlight. Blood doi: 10.1182/blood-2018-10-862243.

  • Armstrong, R. L., Penke, T. J. R., Chao, S. K., Gentile, G. M., Strahl, B. D., Matera, A. G., McKay, D. J. & Duronio, R. J. (2019) H3K9 promotes under-replication of pericentromeric heterochromatin in Drosophila salivary gland polytene chromosomes. Genes. 10(2) E93.

  • Leatham-Jensen, M., Uyehara, C. M., Strahl, B. D., Matera, A. G., Duronio, R. J. & McKay, D., J. (2019) Lysine 27 of replication-independent histone H3.3 is required for Polycomb target gene silencing but not for gene activation. PLoS Genet. 15:e1007932.

  • 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.  Cell Reports. 25:3476-3489.

  • 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.

  • 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.

    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.

  • 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. 

  • 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. Mar 14;10:12.
  • 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.
  • 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.
  • 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 Biology. 12:396-398.
  • 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., Martin, 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.
  • 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.
  • 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.
  • Wozniak, G. G. & Strahl, B. D. (2014) Catalysis-dependent stabilization of Bre1 fine-tunes histone H2B ubiquitylation to regulate gene transcription. Genes & Development. 28:1647-1652.
  • Jha, D. K. & Strahl, B. D. (2014) H3K36 methylation regulates chromatin remodeling and checkpoint activation after DSB. Nature Commun. 5:3965.
  • 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. 42:870-881.

Link to all pubs