p300的乙酰转移酶区域与Sp1的DNA结合结构域在DNA结合上以及通过DNA结合的相互作用的调控。

Regulation of interaction of the acetyltransferase region of p300 and the DNA-binding domain of Sp1 on and through DNA binding.

作者信息

Suzuki T, Kimura A, Nagai R, Horikoshi M

机构信息

Laboratory of Developmental Biology, Department of Cellular Biology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

出版信息

Genes Cells. 2000 Jan;5(1):29-41. doi: 10.1046/j.1365-2443.2000.00302.x.

DOI:10.1046/j.1365-2443.2000.00302.x

PMID:10651903

Abstract

BACKGROUND

The coactivator p300 acts as a transcriptional adaptor for many DNA-binding activators. The finding that p300 possesses intrinsic acetyltransferase activity which, by chemically modifying histone tails affects the nucleosomal environment and transcription, has greatly advanced our understanding of its function. Subsequent recent studies have shown that non-histone proteins are also acetylated. However, one central question which has remained unanswered is how the coactivator/acetyltransferase interacts with DNA-binding activators to modulate their actions.

RESULTS

Here we have demonstrated physical and functional interaction between the acetyltransferase region of p300 and the DNA-binding domain (DBD) of the transcription factor Sp1. This interaction stimulates DNA binding by the DBD of Sp1, which is mediated primarily by physical interaction rather than acetylation, despite acetylation of the DBD of Sp1 by the acetyltransferase region of p300. Furthermore, DNA binding by the DBD of Sp1 inhibits both its association and acetylation by the acetyltransferase region of p300.

CONCLUSIONS

These findings suggest a new role for p300 in regulating promoter access by DNA-binding activators through multiple regulatory interactions.

摘要

背景

共激活因子p300作为许多DNA结合激活因子的转录衔接子发挥作用。p300具有内在乙酰转移酶活性这一发现极大地推进了我们对其功能的理解，该活性通过化学修饰组蛋白尾巴影响核小体环境和转录。随后的近期研究表明非组蛋白也会被乙酰化。然而，一个尚未得到解答的核心问题是共激活因子/乙酰转移酶如何与DNA结合激活因子相互作用以调节它们的作用。

结果

在此我们证明了p300的乙酰转移酶区域与转录因子Sp1的DNA结合结构域（DBD）之间存在物理和功能相互作用。这种相互作用刺激Sp1的DBD与DNA结合，这主要由物理相互作用介导而非乙酰化介导，尽管p300的乙酰转移酶区域可使Sp1的DBD发生乙酰化。此外，Sp1的DBD与DNA结合会抑制其与p300的乙酰转移酶区域的结合及其乙酰化。