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学术报告

　　报告题目：Formation and maintenance of heterochromatin domains in yeast

　　报告人：Xin Bi, Ph.D.

　　 Associate Professor

　　Department of Biology

　　University of Rochester

　　时间：2011年12月12日(星期一)上午10：00

　　地点：生化楼三层中厅

　　主持人：尹玉新教授

　　Abstract

　　The eukaryotic genome is composed of condensed heterochromatin and decondensed euchromatin domains. Heterochromatin plays key roles in genome stability and epigenetic regulation of genome activities, which impacts cell proliferation and differentiation, as well as organismal development and aging. In general, euchromatin allows gene transcription, whereas heterochromatin is transcriptionally silent. The budding yeast Saccharomyces cerevisiae has long served as a highly tractable model organism for studying the structure and function of heterochromatin. Yeast heteochromatin exists at the HML and HMR loci as well as regions adjacent to telomeres. Heterochromatin consists of highly ordered nucleosomes that are hypoacetylated, and its formation is mediated by the propagation of the SIR histone deacetylase complex along chromatin. We demonstrated that the Fun30 and Isw1 chromatin remodeling factors are similarly required for transcriptional silencing at HML, but differentially contribute to the structure and stability of HML heterochromatin. In the absence of Fun30, only a partially silenced chromatin structure is formed at HML. This structure resembles fully silenced heterochromatin in histone hypoacetylation and the association of SIR complex, but differs markedly from both fully silenced and derepressed chromatin structures regarding nucleosome arrangement. We found evidence suggetaing that such a structure represents an intermediate state of heterochromatin that can be converted by Fun30 to the mature state. We also obtained evidence suggesting that Fun30 functions together with, or after, the action of SIR complex. On the other hand, Isw1 is dispensable for the formation of heterochromatin structure, but is instead critically required for maintaining its stability. Therefore, chromatin remodeling factors may remodel nucleosomes during the formation of heterochromatin, or serve to stabilize/ maintain heterochromatin structure. Moreover, we investigated the mechanisms underlying the demarcation of heterochromatin domains, and demonstrated that nucleosome-excluding structures and targeted histone acetyltransferases can both block the spreading of SIR complex, thereby acting as boundaries of heterochromatin domains. Importantly, in higher eukaryotes inclduing humans, chromatin remodleing fatcors inclduing the orthologs of Fun30 and Isw1 are also linked to heterochromatin, and heterochromatin boundaries are aften aslo associated with chromatin disruption and histone acetyltransferases.