Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the set oncoprotein

Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the set oncoprotein
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DOI:
10.1016/s0092-8674(01)00196-9
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发表时间:
2001-01-12
期刊:
影响因子:
64.5
通讯作者:
Chakravarti, D
Chakravarti, D
中科院分区:
生物学1区
文献类型:
--
作者:
Seo, SB;McNamara, P;Chakravarti, D

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p300/CBP和PCAF对组蛋白的乙酰化被认为是转录调控中的关键步骤。为了了解调节组蛋白乙酰化和转录的细胞活动的作用,我们已经纯化和表征了一种多蛋白细胞复合物,该复合物有效地抑制p300/CBP和PCAF的组蛋白乙酰转移酶活性。我们已经绘制了一个新的乙酰转移酶抑制结构域的INHAT(乙酰转移酶抑制剂)复合物,结合组蛋白,并掩盖他们从乙酰转移酶底物。内源性INHAT亚基,包括Set/TAF-I β癌蛋白,在体内与染色质结合,并且当在细胞中转染时可以阻断共激活因子介导的转录。我们建议,组蛋白掩蔽INHAT在染色质修饰中起着调节作用,并作为一种新的转录调控机制。
Acetylation of histones by p300/CBP and PCAF is considered to be a critical step in transcriptional regulation. In order to understand the role of cellular activities that modulate histone acetylation and transcription, we have purified and characterized a multiprotein cellular complex that potently inhibits the histone acetyltransferase activity of p300/CBP and PCAF. We have mapped a novel acetyltransferase-inhibitory domain of this INHAT (inhibitor of acetyltransferases) complex that binds to histones and masks them from being acetyltransferase substrates. Endogenous INHAT subunits, which include the Set/TAF-I beta oncoprotein, associate with chromatin in vivo and can block coactivator-mediated transcription when transfected in cells. We propose that histone masking by INHAT plays a regulatory role in chromatin modification and serves as a novel mechanism of transcriptional regulation.