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标题：Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate
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作者：Stefan Ehrentraut ; Jan M. Weber ; J. Nikolaj Dybowski 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：12
页码：5522-5527
DOI：10.1073/pnas.0909169107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Boundaries between euchromatic and heterochromatic regions until now have been associated with chromatin-opening activities. Here, we identified an unexpected role for histone deacetylation in this process. Significantly, the histone deacetylase (HDAC) Rpd3 was necessary for boundary formation in Saccharomyces cerevisiae. rpd3{Delta} led to silent information regulator (SIR) spreading and repression of subtelomeric genes. In the absence of a known boundary factor, the histone acetyltransferase complex SAS-I, rpd3{Delta} caused inappropriate SIR spreading that was lethal to yeast cells. Notably, Rpd3 was capable of creating a boundary when targeted to heterochromatin. Our data suggest a mechanism for boundary formation whereby histone deacetylation by Rpd3 removes the substrate for the HDAC Sir2, so that Sir2 no longer can produce O-acetyl-ADP ribose (OAADPR) by consumption of NAD+ in the deacetylation reaction. In essence, OAADPR therefore is unavailable for binding to Sir3, preventing SIR propagation.
关键词：gene silencing ; histone deacetylase ; O-acetyl-ADP-ribose ; Sas2 ; Sir3