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两种染色质重塑活性在激素应答启动子激活过程中协同作用。

Two chromatin remodeling activities cooperate during activation of hormone responsive promoters.

作者信息

Vicent Guillermo Pablo, Zaurin Roser, Nacht A Silvina, Li Ang, Font-Mateu Jofre, Le Dily Francois, Vermeulen Michiel, Mann Matthias, Beato Miguel

机构信息

Centre de Regulació Genòmica (CRG), Universitat Pompeu Fabra, Parc de Recerca Biomèdica (PRBB), Barcelona, Spain.

出版信息

PLoS Genet. 2009 Jul;5(7):e1000567. doi: 10.1371/journal.pgen.1000567. Epub 2009 Jul 17.

DOI:10.1371/journal.pgen.1000567
PMID:19609353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2704372/
Abstract

Steroid hormones regulate gene expression by interaction of their receptors with hormone responsive elements (HREs) and recruitment of kinases, chromatin remodeling complexes, and coregulators to their target promoters. Here we show that in breast cancer cells the BAF, but not the closely related PBAF complex, is required for progesterone induction of several target genes including MMTV, where it catalyzes localized displacement of histones H2A and H2B and subsequent NF1 binding. PCAF is also needed for induction of progesterone target genes and acetylates histone H3 at K14, an epigenetic mark that interacts with the BAF subunits by anchoring the complex to chromatin. In the absence of PCAF, full loading of target promoters with hormone receptors and BAF is precluded, and induction is compromised. Thus, activation of hormone-responsive promoters requires cooperation of at least two chromatin remodeling activities, BAF and PCAF.

摘要

类固醇激素通过其受体与激素反应元件（HREs）相互作用，并将激酶、染色质重塑复合物和共调节因子募集到其靶启动子上来调节基因表达。我们在此表明，在乳腺癌细胞中，孕激素诱导包括MMTV在内的多个靶基因需要BAF，而与之密切相关的PBAF复合物则不需要，BAF在其中催化组蛋白H2A和H2B的局部置换以及随后NF1的结合。孕激素靶基因的诱导也需要PCAF，它在K14位点使组蛋白H3乙酰化，这是一种表观遗传标记，通过将复合物锚定到染色质上与BAF亚基相互作用。在没有PCAF的情况下，靶启动子无法被激素受体和BAF完全装载，诱导作用受损。因此，激素反应性启动子的激活需要至少两种染色质重塑活性BAF和PCAF的协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/ed0a1b5d7199/pgen.1000567.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/e99654abef2e/pgen.1000567.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/e2e4eaec7b0e/pgen.1000567.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/680f75c0ca54/pgen.1000567.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/d92d1e9b64f2/pgen.1000567.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/ed0a1b5d7199/pgen.1000567.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/e99654abef2e/pgen.1000567.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/e2e4eaec7b0e/pgen.1000567.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/680f75c0ca54/pgen.1000567.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/d92d1e9b64f2/pgen.1000567.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942f/2704372/ed0a1b5d7199/pgen.1000567.g005.jpg

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