Isoform-specific interaction of HP1 with human TAFII130.

Isoform-specific interaction of HP1 with human TAFII130.
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HP1 与人 TAFII130 的亚型特异性相互作用。

DOI:
10.1073/pnas.092025499
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发表时间:
2002
影响因子:
11.1
通讯作者:
Tanese,Naoko
Tanese,Naoko
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Vassallo,MiloF;Tanese,Naoko

文献摘要

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通用转录因子TFIID促进转录机制向基因启动子的募集,并通过RNA聚合酶II调节转录的起始。hTAFII 130是TFIID的一个组成部分,与多种转录调节蛋白相互作用并作为其共激活因子,包括Sp1和CREB。酵母双杂交筛选已确定hTAFII 130和异染色质蛋白1(HP 1),染色质相关蛋白,其功能已牵连在基因沉默之间的相互作用。我们发现hTAFII 130与HP 1以同种型特异性方式结合:HP 1 α和HP 1 γ与hTAFII 130结合,但不与HP 1 β结合。此外,我们发现HeLa细胞核提取物中内源性hTAFII 130和TFIID组分与谷胱甘肽S-转移酶-HP 1 α和-HP 1 γ相关。hTAFII 130具有五肽HP 1结合基序,hTAFII 130 HP 1盒的突变损害了hTAFII 130与HP 1的相互作用。我们证明Gal 4-HP 1蛋白干扰hTAFII 130介导的转录激活。我们的结果表明HP 1 α和HP 1 γ与hTAPHI 130结合介导转录抑制,支持一种涉及TFIID组分与染色质之间特异性相互作用的转录抑制新模型。
The general transcription factor TFIID facilitates recruitment of the transcription machinery to gene promoters and regulates initiation of transcription by RNA polymerase II. hTAFII130, a component of TFIID, interacts with and serves as a coactivator for multiple transcriptional regulatory proteins, including Sp1 and CREB. A yeast two-hybrid screen has identified an interaction between hTAFII130 and heterochromatin protein 1 (HP1), a chromatin-associated protein whose function has been implicated in gene silencing. We find that hTAFII130 associates with HP1 in an isoform-specific manner: HP1α and HP1γ bind to hTAFII130, but not HP1β. In addition, we show that endogenous hTAFII130 and components of TFIID in HeLa nuclear extracts associate with glutathioneS-transferase-HP1α and -HP1γ. hTAFII130 possesses a pentapeptide HP1-binding motif, and mutation of the hTAFII130 HP1 box compromises the interaction of hTAFII130 with HP1. We demonstrate that Gal4-HP1 proteins interfere with hTAFII130-mediated activation of transcription. Our results suggest that HP1α and HP1γ associate with hTAFII130 to mediate repression of transcription, supporting a new model of transcriptional repression involving a specific interaction between a component of TFIID and chromatin.