Ume1p represses meiotic gene transcription in Saccharomyces cerevisiae through interaction with the histone deacetylase Rpd3p
Ume1p represses meiotic gene transcription in Saccharomyces cerevisiae through interaction with the histone deacetylase Rpd3p
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DOI：
10.1074/jbc.m308632200
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发表时间：
2003-11-07
影响因子：
4.8
通讯作者：
Strich, R
中科院分区：
文献类型：
--
作者：
Mallory, MJ;Strich, R
Ume1p是包括RbAp48在内的一个保守蛋白家族的成员，它与组蛋白脱乙酰基酶相关。与这一发现一致，Ume1p是在芽期酵母营养生长过程中完全抑制减数分裂基因子集所必需的。除了有丝分裂细胞分裂外，这份报告还描述了Ume1p在减数分裂基因抑制中的一个新作用，即在承诺前形成孢子的培养物恢复营养生长。然而，作为减数分裂瞬时转录程序的一部分，Ume1p不是重建抑制所必需的。突变分析表明，Ume1p依赖的抑制需要两个保守结构域(nee box和WD重复基序)。免疫共沉淀研究表明，nee盒和WD重复基序对于正常的Rpd3p结合都是必不可少的。最后，Ume1p-Rpd3p的关联依赖于全局共抑制因子Sin3p。此外，该活性被定位于Sin3p的四个成对的两亲性螺旋结构域之一，这是转录抑制所必需的。这些发现支持Ume1p与Rpd3p结合是其抑制活性所必需的模型。此外，这些结果表明，Rpd3-Ume1p-Sin3p包含介导转录抑制所需的相互依赖的复合体。
Ume1p is a member of a conserved protein family including RbAp48 that associates with histone deacetylases. Consistent with this finding, Ume1p is required for the full repression of a subset of meiotic genes during vegetative growth in budding yeast. In addition to mitotic cell division, this report describes a new role for Ume1p in meiotic gene repression in precommitment sporulating cultures returning to vegetative growth. However, Ume1p is not required to re-establish repression as part of the meiotic transient transcription program. Mutational analysis revealed that two conserved domains (NEE box and a WD repeat motif) are required for Ume1p-dependent repression. Co-immunoprecipitation studies revealed that both the NEE box and the WD repeat motif are essential for normal Rpd3p binding. Finally, Ume1p-Rpd3p association is dependent on the global co-repressor Sin3p. Moreover, this activity was localized to one of the four paired amphipathic-helix domains of Sin3p shown previously to be required for transcriptional repression. These findings support a model that Ume1p binding to Rpd3p is required for its repression activity. In addition, these results suggest that Rpd3-Ume1p-Sin3p comprises an interdependent complex required for mediating transcriptional repression.