主讲人：Robert G. Roeder
讲座时间：14:00 — 15:00
题目：Mechanisms of transcriptional regulation through diverse co-activators
报告人：Robert G. Roeder, Ph.D.
Arnold and Mabel Beckman Professor
Laboratory of Biochemistry and Molecular Biology
The Rockefeller University
Prof.Robert G. Roederis known as a pioneer ineukaryotic transcription. He is the recipient of theGairdner FoundationInternational Award in 2000 and theAlbert Lasker Awardfor Basic Medical Research in 2003. He currently serves as Arnold and Mabel Beckman Professor and Head of the Laboratory of Biochemical and Molecular Biology at The Rockefeller University.He was elected as amember of the National Academy of Sciencesin 1988 and the American Academy of Arts and Sciences in 1995, and a foreign associate member of the European Molecular Biology Organization in 2003.
Transcriptional regulation by gene- and cell-specific DNA-binding factors underlies key events in development, cell differentiation and transformation. However, their effects on specific genes depend upon complex arrays of cofactors (co-activators and co-repressors) whose biochemical mechanisms are not completely understood. These cofactors include both chromatin remodeling/histone modifying factors (e.g., the p300/CBP histone acetyl-transferases and the SET1/MLL H3K4 methyl-transferases) and other factors (e.g., Mediator, TAFs) that facilitate more direct communication between promoter-bound regulatory factors and the general transcription machinery. Emphasizing biochemical studies with cell-free systems reconstituted with recombinant chromatin templates and purified transcription factors, the cooperative functions and mechanism of action of selected co-activators will be discussed in relation to gene regulation by selected activators. This will include recent studies of p300-dependent activation of chromatin templates through novel acylation marks, cooperative functions of p300 and UTX+MLL3/4 complexes in establishment of active enhancers and mechanisms for the de-compaction and activation of higher order (linker histone H1-containing) chromatin templates.
Key publications(since 2004):
2017. DND1 maintains germline stem cells via recruitment of the CCR4-NOT complex to target mRNAs.Nature. Mar 15. doi: 10.1038/nature21690
2016. RNA polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II.Science. 350(6266):1383-6
2013. SET1 and p300 act synergistically, through coupled histone modifications, in transcriptional activation by p53.Cell. 154(2):297-310
2013. A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis.Nature. 500(7460):93-7
2013. H3K4me3 interactions with TAF3 regulate preinitiation complex assembly and selective gene activation.Cell. 152(5):1021-36
2011. Role for Dpy-30 in ES cell-fate specification by regulation of H3K4 methylation within bivalent domains.Cell. 144(4):513-25
2010. The human PAF1 complex acts in chromatin transcription elongation both independently and cooperatively with SII/TFIIS.Cell. 140(4):491-503
2009. RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells.Cell. 137(3):459-71
2006. Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development.Cell. 125(4):761-74.
2006. Synergistic functions of SII and p300 in productive activator-dependent transcription of chromatin templates.Cell. 2006 125(2):275-86
2005. Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF.Cell. 121(6):873-85
2004. E protein silencing by the leukemogenic AML1-ETO fusion protein.Science. 305(5688):1286-9.
2004. Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53.Cell. 117(6):735-48.