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BK21 Program of Bio-Molecular Function Seminar/ Biotechnology Research Center
▶Subject : Role of Elongation Factors and Chromatin Modifying Factors in Transcriptional Activation
▶Speaker : Jaehoon Kim
(Laboratory of Biochemistry and Molecular Biology The Rockefeller University)
▶Date : PM 2:00/May 26/2010
▶Place : Rm 104, Life Science Bldg
Genomic DNA in eukaryotic nuclei is organized within a hierarchical chromatin structure that results in repression of genes by restricting access to the general transcription machinery. Gene activation involves changes in chromatin (nucleosomal) structure that result, in part, from post-translational histone modifications and that increase the accessibility of DNA to transcription factors. The diverse histone modifications that play important roles in transcriptional regulation throughout eukaryotes include histone H2B (H2B) monoubiquitylation, although the precise mechanisms involved in H2B ubiquitylation and the role(s) of ubiquitylated H2B were not fully understood. We have employed rigorous biochemical approaches to reveal the molecular mechanism of H2B ubiquitylation during transcription. We identified the bona-fide H2B ubiquitylation factors (RAD6 and the BRE1 complex as E2 ubiquitin conjugating enzyme and E3 ubiquitin ligase, respectively) in human cells and provided a mechanistic understanding of the process of transcription-coupled H2B ubiquitylation, which was found to involve direct interactions between the ubiquitylation and transcription machineries [Kim et al., (2009) Cell 137, 459-471]. Furthermore, our research provided direct evidence for an intrinsic chromatin transcription elongation activity of the human RNA polymerase II-associated PAF1 complex, a pivotal finding both for understanding efficient transcription through nucleosomes and for explaining the mechanism of H2B ubiquitylation. This work also revealed a strong synergy between the PAF1 complex and elongation factor SII/TFIIS and an underlying mechanism involving direct PAF1-SII interactions and cooperative binding to RNA polymerase II, thus providing first evidence for the cooperative function of distinct transcription elongation factors in chromatin transcription [Kim et al., (2010) Cell 140, 491-503]. Collectively, our work provide ultimate explanations for how H2B ubiquitylation is installed on transcribing genes, why the PAF1 complex is required for H2B ubiquitylation and why H2B ubiquitylation and H3K4 methylation is concentrated on actively transcribing genes. These results also have expanded our understanding of the increasingly complex transcription process and set the stage for detailed analyses of the role of H2B ubiquitylation and its downstream players in specific transcription events.
☎ Inquiry: Prof. Joo Yeon Yoo (279-2346)