【活动预告】染色质与表观遗传学系列讲座第13场——Jerry Workman

主讲人简介 | Speaker Biography

Dr. Jerry Workman is known for his pioneering work uncovering the role of histones in the regulation of gene expression. He obtained his Ph.D. from University of Michigan, Ann Arbor in 1985. Then, he moved to New York City for his postdoctoral fellowship in the lab of Dr. Robert Roeder at Rockefeller University. In Roeder’s lab, Workman showed that transcription factors and nucleosomes compete for DNA sequences to activate or repress genes. In 1992, Workman established his own lab at Pennsylvania State University. In 1998, he became a Howard Hughes Medical Institute Investigator, a position he forfeited to join the Stowers Institute in 2003. At the Stowers Institute, he continued his work in gene regulation in yeast, fruit flies, and mammalian cells. Over the years, Workman maintained a close research collaboration with his wife, the late Susan Abmayr, PhD, who brought fruit fly genetics to his lab.

Workman was one of the first scientists to discover that histones are both important for the packaging of DNA into chromatin and crucial players in the regulation of gene expression. He is also a pioneer of the concept of “transcription co-activators.” His team has identified and characterized various large protein complexes that modify gene expression by causing histones to either loosen or tighten their grips on DNA, leaving it open to enzymes that can efficiently read its code and turn on genes.

More recently, Workman’s focus has been on how signaling, metabolism, and chromatin regulate information contained in the DNA sequence and feedback to cellular events. In 2018, Workman was awarded a Maximizing Investigators’ Research Award (MIRA) from the National Institute of General Medical Sciences based on the lab’s research on chromatin-modifying complexes, including a focus on the multi-subunit complexes SAGA and SWI/SNF.

Jerry Workman教授以其在揭示组蛋白在基因表达调控中的作用的开创性工作而闻名。他于1985年从密歇根大学安娜堡分校获得博士学位。随后他前往纽约，在洛克菲勒大学Robert Roeder教授的实验室进行博士后研究。在Roeder实验室中，Workman教授表明转录因子与核小体竞争DNA序列以激活或抑制基因。1992年，Workman教授在宾夕法尼亚州立大学建立了自己的实验室。1998年，他成为霍华德休斯医学研究所研究员。2003年，他放弃了这一职位，加入了密苏里州斯托瓦斯医学研究所。在斯托瓦斯研究所，他继续使用酵母、果蝇和哺乳动物细胞为材料进行基因调控相关的研究。多年来，Workman教授与他的妻子、已故的Susan Abmayr教授一直保持着密切的研究合作，后者将果蝇遗传学带入了他的实验室。

Workman教授是最早发现组蛋白除了将DNA包装成染色质外还在基因表达调控中起关键作用的科学家之一。他也是“转录共激活因子”概念的先驱之一。他的团队确定并表征了多种大型蛋白质复合物，这些复合物通过使组蛋白放松或收紧对DNA 的控制，使DNA对可以有效读取其序列并激活基因的酶开放，以此来改变基因表达。

近年来，Workman教授的重点是信号通路、代谢途径和染色质如何调控DNA序列中包含的信息以及对细胞事件的反馈。2018年，Workman教授获得了美国国立卫生研究院颁发的“最大化研究者研究奖(MIRA)”。该奖项的获得主要是由于实验室对染色质修饰复合物的研究，包括对多亚基复合物SAGA和SWI/SNF的研究。

Research in my laboratory characterized the dynamic interactions of transcription factors with nucleosomes, discovered and characterized multiple histone acetyltransferase complexes, participated in the discovery and analysis of the Swi/Snf chromatin remodeling complex and discovered the Set2/Rpd3S pathway. More recent studies have been focused on the role of chromatin and chromatin-modifying proteins in signaling for cellular processes. For example, histone H3T11 phosphorylation is a requisite histone modification for the diauxic shift (switch from fermentation to respiration) in yeast and links cytoplasmic nutrient signaling to the transcriptional responses to nutrient stress. The mammalian SETD2 Histone H3K36 methyltransferase has been implicated in both transcriptional regulation and RNA processing (splicing). Our recent studies provide mechanistic insights into how SETD2 connects transcriptional elongation, histone H3K36 methylation and RNA splicing.

1) Bhattacharya S, Levy MJ, Zhang N, Li H, Florens L, Washburn MP, Workman JL. The methyltransferase SETD2 couples transcription and splicing by engaging mRNA processing factors through its SHI domain. Nat Commun. 2020;12:1443. doi: 1410.1038/s41467-41021-21663-w.

2) Soffers JHM, Li X, Saraf A, Seidel CW, Florens L, Washburn MP, Abmayr SM, Workman JL. Characterization of a metazoan ADA acetyltransferase complex. Nucleic Acids Res. 2019;47:3383-3394.

3) Suganuma T, Swanson SK, Gogol MM, Garrett TJ, Conkright-Fincham J, Florens L, Washburn MP, Workman JL. MPTAC determines APP fragmentation via sensing sulfur amino acid catabolism. Cell reports. 2018;24 (6), 1585-1596

4) Oh S, Suganuma T, Gogol, MM, Workman JL. Histone H3 threonine 11 phosphorylation by Sch9 and CK2 regulates chronological lifespan by controlling the nutritional stress response. Elife 7.2018;e36157.

5) Dutta A, Sardiu M, Gogol M, Gilmore J, Zhang D, Florens L, Abmayr SM, Washburn MP, Workman JL. Composition and function of mutant Swi/Snf complexes. Cell Rep. 2017;18:2124-2134.

6) Li S, Swanson SK, Gogol M, Florens L, Washburn MP, Workman JL, Suganuma T. Serine and SAM responsive complex SESAME regulates histone modification crosstalk by sensing cellular metabolism. Mol Cell. 2015;60:408-421.