Nucleosome dynamics: HMGB1 relaxes canonical nucleosome structure to facilitate estrogen receptor binding.

Nucleosome dynamics: HMGB1 relaxes canonical nucleosome structure to facilitate estrogen receptor binding.
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DOI:
10.1093/nar/gks815
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发表时间:
2012-11-01
影响因子:
14.9
通讯作者:
Scovell WM
Scovell WM
中科院分区:
生物学2区
文献类型:
--
作者:
Joshi SR;Sarpong YC;Peterson RC;Scovell WM

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高迁移率族蛋白1(HMGB1)与DNA和染色质相互作用,影响转录、DNA修复和重组的调控。我们发现HMGB1以非酶促的、不依赖ATP的方式改变了典型核小体(N)的结构和稳定性。虽然雌激素受体(ER)不与核小体内的共有雌激素反应元件结合,但HMGB1重组核小体以促进强ER结合。分离的HMGB1重组核小体(N′和N″)保持稳定,并表现出明显不同于典型核小体的特征。这些发现补充了先前的研究,这些研究表明(i)HMGB1刺激雌激素反应元件的体内转录激活,以及(ii)通过siRNA敲低HMGB1表达急剧降低转录激活。研究结果表明,HMGB1作用机制的一个方面涉及核小体的重组,似乎放松了核小体内的结构约束。
High mobility group protein 1 (HMGB1) interacts with DNA and chromatin to influence the regulation of transcription, DNA repair and recombination. We show that HMGB1 alters the structure and stability of the canonical nucleosome (N) in a nonenzymatic, ATP-independent manner. Although estrogen receptor (ER) does not bind to its consensus estrogen response element within a nucleosome, HMGB1 restructures the nucleosome to facilitate strong ER binding. The isolated HMGB1-restructured nucleosomes (N′ and N″) remain stable and exhibit characteristics distinctly different from the canonical nucleosome. These findings complement previous studies that showed (i) HMGB1 stimulates in vivo transcriptional activation at estrogen response elements and (ii) knock down of HMGB1 expression by siRNA precipitously reduced transcriptional activation. The findings indicate that one aspect of the mechanism of HMGB1 action involves a restructuring of the nucleosome that appears to relax structural constraints within the nucleosome.
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