CoREST is an integral component of the CoREST-human histone deacetylase complex

CoREST is an integral component of the CoREST-human histone deacetylase complex
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DOI:
10.1073/pnas.98.4.1454
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发表时间:
2001-02-13
影响因子:
11.1
通讯作者:
Schreiber, SL
Schreiber, SL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
You, A;Tong, JK;Schreiber, SL

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在这里,我们描述了组蛋白脱乙酰酶(HDAC)复合物的组成部分,我们称之为CoREST-HDAC复合物。CoREST-HDAC由与先前表征的含HDAC 1/2的复合物(例如mSin 3和核小体重塑和脱乙酰化(NRD,也称为NRD,NuRD)复合物)不同的多肽组成。有趣的是,我们没有在该复合物中观察到RbAp 46和RbAp 48,尽管这些蛋白质已经在所有先前鉴定的复合物中观察到,并且被认为是HDAC 1/2核心的一部分。我们确定了转录辅阻遏物CoREST和一种与多胺氧化酶同源的蛋白质作为CoREST-HDAC的组成部分。CoREST的HDAC 1/2相互作用区域被映射到含有SANT结构域的179个氨基酸的区域,SANT结构域是在其他HDAC 1/2相互作用蛋白如NCoR、MTA 1和MTA 2中发现的结构域。此外,我们证明了CoREST的辅阻遏功能取决于该区域。虽然CoREST最初被克隆为REST(RE 1沉默转录因子/神经限制性沉默因子)的辅阻遏物,但我们没有发现八锌指REST转录因子作为该复合物中相互作用伙伴存在的证据;然而,我们确实发现了含有八个锌指的推定致癌基因ZNF 217的关联证据。
Here we describe the components of a histone deacetylase (HDAC) complex that we term the CoREST-HDAC complex. CoREST-HDAC is composed of polypeptides distinct from previously characterized HDAC1/2-containing complexes such as the mSin3 and nucleosome remodeling and deacetylating (NRD, also named NURD, NuRD) complex. Interestingly, we do not observe RbAp46 and RbAp48 in this complex, although these proteins have been observed in all previously identified complexes and are thought to be part of an HDAC1/2 core. We identify the transcriptional corepressor CoREST and a protein with homology to polyamine oxidases as components of CoREST-HDAC. The HDAC1/2-interacting region of CoREST is mapped to a 179-aa region containing a SANT domain, a domain found in other HDAC1/2-interacting proteins such as NCoR, MTA1, and MTA2. Furthermore, we demonstrate that the corepressor function of CoREST depends on this region. Although CoREST initially was cloned as a corepressor to REST (RE1 silencing transcription factor/neural restrictive silencing factor), we find no evidence for the existence of the eight-zinc finger REST transcription factor as an interacting partner in this complex; however, we do find evidence for association of the putative oncogene ZNF 217 that contains eight zinc fingers.