Multiple mechanisms of transcriptional repression by YY1
Multiple mechanisms of transcriptional repression by YY1
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DOI：
10.1128/mcb.17.7.3723
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发表时间：
1997-07-01
影响因子：
5.3
通讯作者：
Shi, Y
中科院分区：
文献类型：
--
作者：
Galvin, KM;Shi, Y
YY 1基因C端的四个GLI-Kruppel型锌指结构域被认为是一个转录抑制结构域，以往的研究报道提出了这一锌指结构域的DNA弯曲和激活子淬灭机制，此外，以往的工作表明p300和CBP可能参与YY 1基因的转录抑制，我们分析了这些可能的锌指结构域的转录抑制模型，每个锌指在阻遏和DNA结合功能中的作用通过使用结构和功能方法来确定。我们发现YY 1的锌指2在DNA结合和转录抑制中起着核心作用，然而，对一组YY 1突变体的调查表明这两种功能可以分离，这与DNA弯曲抑制模型相反。我们的研究表明，YY 1与CREB共激活子p300之间的物理相互作用不足以抑制CREB介导的转录。我们的研究表明，YY 1作为激活子特异性抑制子发挥作用，CTF-1介导的转录抑制可能通过YY 1与该激活子之间的直接物理相互作用来实现。物理相互作用不是YY 1抑制Sp1和CREB介导的转录所必需的。相反，这种抑制可能反映了YY 1干扰这些激活物与其靶点之间在一般转录机制中的通讯的能力。总之，我们的研究结果表明YY 1采用多种机制来实现激活物特异性抑制。
The four C-terminal GLI-Kruppel type zinc fingers of YY1 have been identified as a transcriptional repression domain, Previous reports have proposed DNA-bending and activator-quenching mechanisms for this zinc finger-mediated repression, In addition, previous work indicated that p300 and CBP might be involved in YY1-mediated repression, We have analyzed these possible models for the zinc finger-mediated repression, The role of each zinc finger in the repression and DNA-binding functions was determined by using a structure-and-function approach. We show that zinc finger 2 of YY1 plays a central role in both DNA binding and transcriptional repression, However, a survey of a panel of YY1 mutants indicates that these two functions can be separated, which argues against the DNA-bending model for repression. We show that the physical interaction between YY1 and p300, a coactivator for CREB, is not sufficient for repression of CREB-mediated transcription, Our studies indicate that YY1 functions as an activator-specific repressor, Repression of CTF-1-directed transcription mag he accomplished through direct physical Interaction between YY1 and this activator, In contrast, physical interaction Is not necessary for YY1 to repress Sp1- and CREB-mediated transcription. Rather, the repression likely reflects an ability of YY1 to interfere with communication between these activators and their targets within the general transcription machinery, Taken together, our results suggest that YY1 employs multiple mechanisms to achieve activator-specific repression.