Brian D. Strahl

Last updated
Brian David Strahl
Brian strahl photo.jpg
Brian D. Strahl in 2024
Born1970
NationalityAmerican
Known forHistone code hypothesis & Research of histone modifications
Scientific career
FieldsEpigenetics
InstitutionsUniversity of North Carolina at Chapel Hill
Academic advisorsC. David Allis
Website https://strahl-lab.org/

Brian David Strahl (born 1970) is an American biochemist and molecular biologist. [1] He is currently a professor in the Department of Biochemistry & Biophysics [2] at the University of North Carolina at Chapel Hill. [3] Strahl is known for his research in the field of chromatin biology and histone modifications. Strahl, with C. David Allis proposed the “histone code hypothesis”. [4]

Contents

Early life and education

Strahl was born in Buffalo, New York and raised in Albuquerque, New Mexico. He moved to Chapel Hill, North Carolina in 1980 when his father went to medical school at the University of North Carolina at Chapel Hill. Strahl entered the University of North Carolina at Greensboro [5] in 1988, where he double majored in Chemistry and Biology. Strahl joined the Department of Biochemistry at North Carolina State University [6] and received his PhD in 1998 under the supervision of Dr. William L. Miller. [7] At North Carolina State University, Strahl defined mechanisms for how the Follicle-Stimulating Hormone-Beta (FSHß) gene is regulated at the transcriptional level. [8] [9] In 1998, Strahl performed postdoctoral studies under the mentorship of Dr. C. David Allis at the University of Virginia’s Department of Biochemistry and Molecular Genetics.

Career

In 2001, Strahl joined the University of North Carolina at Chapel Hill as an assistant professor in the Department of Biochemistry and Biophysics. He was promoted to associate professor in 2008 and full professor in 2014. He also holds an appointment at UNC’s Lineberger Comprehensive Cancer Center [10] and is a faculty member in the Curriculum in Genetics and Molecular Biology. [11] Additionally, Strahl also serves as the faculty director of the UNC High-Throughput Peptide Synthesis and Array Core Facility [12] From 2016 to 2020, he served as the Vice Chair of the Department of Biochemistry & Biophysics at UNC. [13] From 2020 to 2022, he stepped into the role of Interim Chair of Biochemistry and Biophysics. [14] Since 2023, Strahl has held the position of Assistant Dean for Research in the Office of Research at the University of North Carolina School of Medicine. [15] The primary mission of the Office of Research is to develop and implement a strategic plan for research in the School of Medicine(reference). The UNC School of Medicine selected Strahl as an Oliver Smithies Investigator in recognition of his research contributions. [16] This annual award recognizes senior faculty members who have gained international recognition for their work. Since 2015, Strahl has directed UNC's Program on Chromatin and Epigenetics, [17] aiming to understand the complex language of epigenetic regulation. The program seeks to advance human health and address diseases. [18] Stahl is also co-founder of EpiCypher, [19] Inc. [20] – a company known for services for chromatin biology and epigenetics research.

Research and Discoveries

Strahl is a pioneer in the field of epigenetics, with contributions to the study of Chromatin biology. As a postdoctoral fellow in C. David Allis’ laboratory, helped to establish the identity of the first lysine and arginine histone methyltransferases and how they contribute to transcriptional activation and heterochromatin formation. Some examples include the discovery of the first histone methyltransferases that target lysine 4 (Set1), [21] lysine 9 (SUV39H1), [22] and lysine 36 of histone H3 (Set2/SETD2) [23] and arginine 3 of histone H4 (PRMT1). [24] Strahl also helped to develop the first antibodies for methylated histones in the Allis laboratory. In 2000, Strahl and Allis put forward the idea of the “histone code hypothesis”, which aimed to explain how multiple histone modifications function together to control chromatin structure and function. [4] The early years of the Strahl laboratory, research focused on the roles of histone methylation and histone ubiquitylation in gene transcription. He linked histone H2B ubiquitylation to the regulation of H3 lysine 79 methylation and in transcriptional elongation [25] [26] and determined how H3 lysine 36 methylation is coupled to RNA Polymerase II [27] and repressive chromatin during transcription elongation. [28] His group also defined the key roles of several histone chaperones (e.g., Spt6) that function in transcription [29] [30] In more recent years, Strahl turned his attention to how chromatin-associated proteins engage histones and their modifications. Through the development of a peptide microarray platform, [31] his group uncovered mechanisms of DNA methylation maintenance [32] [33] and defined modes of chromatin engagement by distinct families of histone-binding effector domains. [34] [35] [36] Recent work has also turned to how recently defined effector domains, including the YEATS domain, contribute to chromatin function and metabolic transcription [37] [38]

References

  1. "Brian D. Strahl". Biochemistry and Biophysics.
  2. "UNC Department of Biochemistry and Biophysics". Biochemistry and Biophysics.
  3. "The University of North Carolina at Chapel Hill". The University of North Carolina at Chapel Hill. March 27, 2024.
  4. 1 2 Strahl, Brian D.; Allis, C. David (January 26, 2000). "The language of covalent histone modifications" . Nature. 403 (6765): 41–45. Bibcode:2000Natur.403...41S. doi:10.1038/47412. PMID   10638745 via www.nature.com.
  5. "Home Page". UNC Greensboro.
  6. "North Carolina State University". NC State University.
  7. "William Miller". Molecular and Structural Biochemistry.
  8. Strahl, Brian D.; Huang, Huey-Jing; Sebastian, Joseph; Ghosh, Basavdutta R.; Miller, William L. (1998). "Transcriptional Activation of the Ovine Follicle-Stimulating Hormone β-Subunit Gene by Gonadotropin-Releasing Hormone: Involvement of Two Activating Protein-1-Binding Sites and Protein Kinase C**This work was supported by the North Carolina State University Agricultural Research Service, NICHD Grant 34863, and the Mellon Foundation" . Endocrinology. 139 (11): 4455–4465. doi:10.1210/endo.139.11.6281. PMID   9794452.
  9. Strahl, Brian D.; Huang, Huey-Jing; Pedersen, Norma R.; Wu, Joyce C.; Ghosh, Basavdutta R.; Miller, William L. (1997). "Two Proximal Activating Protein-1-Binding Sites Are Sufficient to Stimulate Transcription of the Ovine Follicle-Stimulating Hormone-β Gene" . Endocrinology. 138 (6): 2621–2631. doi:10.1210/endo.138.6.5205. PMID   9165057.
  10. "Brian D. Strahl". UNC Lineberger.
  11. "GMB Faculty | Curriculum in Genetics and Molecular Biology". gmb.unc.edu.
  12. "Contact | UNC High-Throughput Peptide Synthesis and Array Facility". www.med.unc.edu.
  13. "Epigenetics: Brian Strahl, Ph.D., Faculty Spotlight". October 2018.
  14. "Strahl named Interim Chair, Department of Biochemistry and Biophysics". 9 April 2020.
  15. "Strahl Named Interim Assistant Dean for Research". School of Medicine Intranet. June 7, 2023.
  16. Clabo, Carolyn (January 31, 2018). "Strahl named Smithies Investigator". Biochemistry and Biophysics.
  17. "Faculty | Chromatin and Epigenetics Program". www.med.unc.edu.
  18. "Chromatin and Epigenetics Program". www.med.unc.edu.
  19. "EpiCypher Scientific Founders". www.epicypher.com.
  20. "EpiCypher | Bringing Epigenetics to Life | For scientists. By scientists". www.epicypher.com.
  21. Briggs, S. D.; Bryk, M.; Strahl, B. D.; Cheung, W. L.; Davie, J. K.; Dent, S. Y.; Winston, F.; Allis, C. D. (2001). "Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae". Genes & Development. 15 (24): 3286–3295. doi:10.1101/gad.940201. PMC   312847 . PMID   11751634.
  22. Rea, S.; Eisenhaber, F.; O'Carroll, D.; Strahl, B. D.; Sun, Z. W.; Schmid, M.; Opravil, S.; Mechtler, K.; Ponting, C. P.; Allis, C. D.; Jenuwein, T. (2000). "Regulation of chromatin structure by site-specific histone H3 methyltransferases". Nature. 406 (6796): 593–599. doi:10.1038/35020506. PMID   10949293.
  23. Strahl, B. D.; Grant, P. A.; Briggs, S. D.; Sun, Z. W.; Bone, J. R.; Caldwell, J. A.; Mollah, S.; Cook, R. G.; Shabanowitz, J.; Hunt, D. F.; Allis, C. D. (2002). "Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression". Molecular and Cellular Biology. 22 (5): 1298–1506. doi:10.1128/MCB.22.5.1298-1306.2002. PMC   134702 . PMID   11839797.
  24. Strahl, B. D.; Briggs, S. D.; Brame, C. J.; Caldwell, J. A.; Koh, S. S.; Ma, H.; Cook, R. G.; Shabanowitz, J.; Hunt, D. F.; Stallcup, M. R.; Allis, C. D. (2001). "Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1". Current Biology. 11 (12): 996–1000. Bibcode:2001CBio...11..996S. doi: 10.1016/s0960-9822(01)00294-9 . PMID   11448779.
  25. Briggs, Scott D.; Xiao, Tiaojiang; Sun, Zu-Wen; Caldwell, Jennifer A.; Shabanowitz, Jeffrey; Hunt, Donald F.; Allis, C. David; Strahl, Brian D. (August 26, 2002). "Trans-histone regulatory pathway in chromatin". Nature. 418 (6897): 498. doi:10.1038/nature00970. PMID   12152067 via www.nature.com.
  26. Xiao, T.; Kao, C. F.; Krogan, N. J.; Sun, Z. W.; Greenblatt, J. F.; Osley, M. A.; Strahl, B. D. (2005). "Histone H2B ubiquitylation is associated with elongating RNA polymerase II". Molecular and Cellular Biology. 25 (2): 637–651. doi:10.1128/MCB.25.2.637-651.2005. PMC   543430 . PMID   15632065.
  27. 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 & Development. 17 (5): 654–663. doi:10.1101/gad.1055503. PMC   196010 . PMID   12629047.
  28. Keogh, M. C.; Kurdistani, S. K.; Morris, S. A.; Ahn, S. H.; Podolny, V.; Collins, S. R.; Schuldiner, M.; Chin, K.; Punna, T.; Thompson, N. J.; Boone, C.; Emili, A.; Weissman, J. S.; Hughes, T. R.; Strahl, B. D.; Grunstein, M.; Greenblatt, J. F.; Buratowski, S.; Krogan, N. J. (2005). "Cotranscriptional Set2 Methylation of Histone H3 Lysine 36 Recruits a Repressive Rpd3 Complex - ScienceDirect". Cell. 123 (4): 593–605. doi: 10.1016/j.cell.2005.10.025 . PMID   16286008.
  29. 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. doi:10.1093/nar/gkt1003. PMC   3902893 . PMID   24163256.
  30. 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 - ScienceDirect". Molecular Cell. 70 (6): 1054–1066.e4. doi:10.1016/j.molcel.2018.05.020. PMC   6323640 . PMID   29932900.
  31. Rothbart, S. B.; Krajewski, K.; Strahl, B. D.; Fuchs, S. M. (2012). "Peptide Microarrays to Interrogate the "Histone Code"". Nucleosomes, Histones & Chromatin Part A. Methods in Enzymology. Vol. 512. pp. 107–135. doi:10.1016/B978-0-12-391940-3.00006-8. ISBN   978-0-12-391940-3. PMC   3741997 . PMID   22910205.
  32. Rothbart, S. B.; Krajewski, K.; Nady, N.; Tempel, W.; Xue, S.; Badeaux, A. I.; Barsyte-Lovejoy, D.; Martinez, J. Y.; Bedford, M. T.; Fuchs, S. M.; Arrowsmith, C. H.; Strahl, B. D. (2012). "Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation". Nature Structural & Molecular Biology. 19 (11): 1155–1160. doi:10.1038/nsmb.2391. PMC   3492551 . PMID   23022729.
  33. Rothbart, S. B.; Dickson, B. M.; Ong, M. S.; Krajewski, K.; Houliston, S.; Kireev, D. B.; Arrowsmith, C. H.; Strahl, B. D. (2013). "Multivalent histone engagement by the linked tandem Tudor and PhD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation". Genes & Development. 27 (11): 1288–1298. doi:10.1101/gad.220467.113. PMC   3690401 . PMID   23752590.
  34. Shanle, E. K.; Shinsky, S. 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 . PMC   5348760 . PMID   28293301.
  35. Jain, K.; Fraser, C. S.; Marunde, M. R.; Parker, M. M.; Sagum, C.; Burg, J. M.; Hall, N.; Popova, I. K.; Rodriguez, K. L.; Vaidya, A.; Krajewski, K.; Keogh, M. C.; Bedford, M. T.; Strahl, B. D. (2020). "Characterization of the plant homeodomain (PHD) reader family for their histone tail interactions". Epigenetics & Chromatin. 13 (1): 3. doi: 10.1186/s13072-020-0328-z . PMC   6979384 . PMID   31980037.
  36. Jain, K.; Marunde, M. R.; Burg, J. M.; Gloor, S. L.; Joseph, F. M.; Poncha, K. F.; Gillespie, Z. B.; Rodriguez, K. L.; Popova, I. K.; Hall, N. W.; Vaidya, A.; Howard, S. A.; Taylor, H. F.; Mukhsinova, L.; Onuoha, U. C.; Patteson, E. F.; Cooke, S. W.; Taylor, B. C.; Weinzapfel, E. N.; Cheek, M. A.; Meiners, M. J.; Fox, G. C.; Namitz KEW; Cowles, M. W.; Krajewski, K.; Sun, Z. W.; Cosgrove, M. S.; Young, N. L.; Keogh, M. C.; Strahl, B. D. (2023). "An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability". eLife. 12. doi: 10.7554/eLife.82596 . PMC   10229121 . PMID   37204295.
  37. Gowans, Graeme J.; Bridgers, Joseph B.; Zhang, Jibo; Dronamraju, Raghuvar; Burnetti, Anthony; King, Devin A.; Thiengmany, Aline V.; Shinsky, Stephen A.; Bhanu, Natarajan V.; Garcia, Benjamin A.; Buchler, Nicolas E.; Strahl, Brian D.; Morrison, Ashby J. (19 December 2019). "Recognition of Histone Crotonylation by Taf14 Links Metabolic State to Gene Expression - ScienceDirect". Molecular Cell. 76 (6): 909–921.e3. doi:10.1016/j.molcel.2019.09.029. PMC   6931132 . PMID   31676231.
  38. Zhang, J.; Gundu, A.; Strahl, B. D. (2021). "Recognition of acetylated histone by Yaf9 regulates metabolic cycling of transcription initiation and chromatin regulatory factors". Genes & Development. 35 (23–24): 1678–1692. doi:10.1101/gad.348904.121. PMC   8653784 . PMID   34819351.