Histone deacetylases associated with the mSin3 corepressor mediate Mad transcriptional repression
Histone deacetylases associated with the mSin3 corepressor mediate Mad transcriptional repression
复制标题
DOI：
10.1016/s0092-8674(00)80215-9
复制
发表时间：
1997-05-02
期刊：
影响因子：
64.5
通讯作者：
Eisenman, RN
中科院分区：
文献类型：
--
作者：
Laherty, CD;Yang, WM;Eisenman, RN
Mad-Max异二聚体的转录抑制需要Mad与辅阻遏物mSin 3A/B相互作用。Sin3p、S. mSin 3的酿酒酵母同源物，在与Rpd 3 p相同的途径中起作用，Rpd 3 p是与最近鉴定的两种哺乳动物组蛋白脱乙酰酶HDAC 1和HDAC 2相关的蛋白质。HDAC 2结合需要能够介导转录抑制的mSin 3A的保守区域。此外，Mad 1与mSin 3和HDAC 2形成复合物，该复合物含有组蛋白脱乙酰酶活性。曲古抑菌素A是一种组蛋白去乙酰化酶抑制剂，可消除Mad抑制。我们认为，Mad-Max的功能是通过招募mSin 3-HDAC辅阻遏物复合物使核小体组蛋白脱乙酰化，从而改变染色质结构，阻断转录。
Transcriptional repression by Mad-Max heterodimers requires interaction of Mad with the corepressors mSin3A/B. Sin3p, the S. cerevisiae homolog of mSin3, functions in the same pathway as Rpd3p, a protein related to two recently identified mammalian histone deacetylases, HDAC1 and HDAC2 Here, we demonstrate that mSin3A and HDAC1/2 are associated in vivo. HDAC2 binding requires a conserved region of mSin3A capable of mediating transcriptional repression. In addition, Mad1 forms a complex with mSin3 and HDAC2 that contains histone deacetylase activity. Trichostatin A, an inhibitor of histone deacetylases, abolishes Mad repression. We propose that Mad-Max functions by recruiting the mSin3-HDAC corepressor complex that deacetylates nucleosomal histones, producing alterations in chromatin structure that block transcription.