RELIEF OF YY1 TRANSCRIPTIONAL REPRESSION BY ADENOVIRUS E1A IS MEDIATED BY E1A-ASSOCIATED PROTEIN P300
RELIEF OF YY1 TRANSCRIPTIONAL REPRESSION BY ADENOVIRUS E1A IS MEDIATED BY E1A-ASSOCIATED PROTEIN P300
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DOI：
10.1101/gad.9.10.1188
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发表时间：
1995-05-15
影响因子：
10.5
通讯作者：
SHI, Y
中科院分区：
文献类型：
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作者：
LEE, JS;GALVIN, KM;SHI, Y
YY1在转录起始位点上游结合时抑制转录。这种抑制可由腺病毒E1A缓解。在这里，我们提供了遗传证据，证明E1A缓解YY1抑制的能力受到影响E1A与其相关蛋白p300结合的突变的损害。这表明E1A可能通过结合p300来调节YY1的抑制活性，p300可能与YY1物理络合。通过几种独立的方法在体内证明了YY1/p300蛋白复合物，YY1相互作用域被映射到p300的羧基末端区域，与e1a结合位点不同。与E2F/RB不同，YY1/p300复合物不会被e1a破坏。利用重组p300进行的功能研究明确表明，p300能够通过YY1介导e1a诱导的转录激活。综上所述，这些结果首次揭示了E1A靶向的YY1/p300复合物，并证明了p300在介导YY1和E1A之间相互作用中的作用。因此，我们的数据确定了YY1是p300的伴侣蛋白，并揭示了缓解由E1A介导的YY1抑制的分子机制。
YY1 represses transcription when bound upstream of transcriptional initiation sites. This repression can be relieved by adenovirus E1A. Here, we present genetic evidence that the ability of E1A to relieve YY1 repression was impaired by mutations that affect E1A binding to its associated protein p300. This suggests that E1A may modulate the repressor activity of YY1 by binding to p300, which may be physically complexed with YY1. A YY1/p300 protein complex in vivo was demonstrated by several independent approaches, and the YY1-interacting domain was mapped to the carboxy-terminal region of p300, distinct from the E1A-binding site. Unlike E2F/RB, the YY1/p300 complex is not disrupted by E1A. functional studies using recombinant p300 demonstrated unequivocally that p300 is capable of mediating E1A-induced transcriptional activation through YY1. Taken together, these results reveal, for the first time, a YY1/p300 complex that is targeted by E1A and demonstrate a function for p300 in mediating interactions between YY1 and E1A. Our data thus identify YY1 as a partner protein for p300 and uncover a molecular mechanism for the relief of YY1-mediated repression by E1A.