RIP140 in thyroid hormone-repression and chromatin remodeling of Crabp1 gene during adipocyte differentiation.

RIP140 in thyroid hormone-repression and chromatin remodeling of Crabp1 gene during adipocyte differentiation.
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DOI:
10.1093/nar/gkp780
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发表时间:
2009-11
影响因子:
14.9
通讯作者:
Wei LN
Wei LN
中科院分区:
生物学2区
文献类型:
--
作者:
Park SW;Huang WH;Persaud SD;Wei LN

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在 3T3-L1 细胞中,细胞视黄酸结合蛋白 1 (Crabp1) 基因受到甲状腺激素 (T3) 的双相(增殖与分化)调节。本研究检测脂肪细胞分化过程中 Crabp1 基因的 T3 抑制。 Crabp1 的 T3 抑制需要受体相互作用蛋白 140 (RIP140)。在分化过程中,Crabp1启动子及其上游区域的并置染色质构型得以维持,但跨越甲状腺激素反应元件到转录起始位点的6个核小体双向滑动,第三个核小体在整个分化过程中保持在相同位置。在基础启动子上,RIP140 取代共激活子 GRIP1 和 PCAF,并与 CtBP1、HDAC3 和 G9a 形成抑制复合物。该启动子上最初的活性染色质标记、组蛋白修饰 H3-Ac 和 H3K4-me3 减弱,而抑制性染色质标记、H3K9-me3 和 H3K27-me3 修饰以及 G9a、HP1α、HP1γ 和 H1 的募集则增强。这是第一项研究在激素抑制阶段双向调节激素靶基因的染色质重塑,并为 RIP140 在染色质重塑中抑制激素靶基因表达的功能作用提供了证据。
Cellular retinoic acid binding protein 1 (Crabp1) gene is biphasically (proliferation versus differentiation) regulated by thyroid hormone (T3) in 3T3-L1 cells. This study examines T3-repression of Crabp1 gene during adipocyte differentiation. T3 repression of Crabp1 requires receptor interacting protein 140 (RIP140). During differentiation, the juxtaposed chromatin configuration of Crabp1 promoter with its upstream region is maintained, but the 6-nucleosomes spanning thyroid hormone response element to transcription initiation site slide bi-directionally, with the third nucleosome remaining at the same position throughout differentiation. On the basal promoter, RIP140 replaces coactivators GRIP1 and PCAF and forms a repressive complex with CtBP1, HDAC3 and G9a. Initially active chromatin marks on this promoter, histone modifications H3-Ac and H3K4-me3, are weakened whereas repressive chromatin marks, H3K9-me3 and H3K27-me3 modification and recruitment of G9a, HP1α, HP1γ and H1, are intensified. This is the first study to examine chromatin remodeling, during the phase of hormone repression, of a bi-directionally regulated hormone target gene, and provides evidence for a functional role of RIP140 in chromatin remodeling to repress hormone target gene expression.
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