Chromatin context dominates estrogen regulation of pS2 gene expression.

Chromatin context dominates estrogen regulation of pS2 gene expression.
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DOI:
10.1016/j.yexcr.2008.07.006
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发表时间:
2008-09-10
影响因子:
3.7
通讯作者:
Murdoch FE
Murdoch FE
中科院分区:
医学3区
文献类型:
--
作者:
Oduro AK;Fritsch MK;Murdoch FE

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染色质结构和转录因子活性共同决定基因的转录水平。我们对这些因素中的每一个在特定基因中的相对贡献的理解是有限的。我们研究了改变染色质环境对雌激素反应性pS2启动子活性的影响。我们创建了稳定的细胞系,其中pS2启动子除了位于其天然位点外,还位于另一个染色质位点。两种启动子都对雌激素受体α(ERα)募集有雌激素反应,但转录仅在天然位点可诱导。在重组位点,转录是高的和组成型的。与载体处理的细胞中的天然位点相比,在重组位点观察到组蛋白H3和H4乙酰化(acH3和acH4)以及组蛋白H3水平上的三甲基化赖氨酸4更高。抑制组蛋白去乙酰化酶(HDAC)导致acH4增加,但acH3、ERα结合和天然pS2位点的基础转录仅适度增加。抑制HDAC对重组位点的转录没有影响。这些数据表明,高活性的染色质不仅允许转录,而且可以覆盖在诱导型启动子处对转录因子的需求。
Chromatin structure and transcription factor activity collaborate to set the transcription level of a gene. Our understanding of the relative contributions of each of these factors at a specific gene is limited. We studied the effects of an altered chromatin environment on the activity of the estrogen responsive pS2 promoter. We created stable cell lines with the pS2 promoter situated in an alternative chromatin site in addition to it being in its native site. Both promoters were estrogen responsive for estrogen receptor alpha (ERα) recruitment, but transcription was inducible only at the native site. At the recombinant site, transcription was high and constitutive. Higher histone H3 and H4 acetylation (acH3 and acH4), as well as trimethylated lysine 4 on histone H3 levels, were observed at the recombinant site compared to the native site in vehicle treated cells. Inhibition of histone deacetylases (HDACs) resulted in increased acH4, but only modest increases in acH3, ERα binding and basal transcription at the native pS2 site. Inhibiting HDACs had no effect on transcription from the recombinant site. These data suggest that highly active chromatin is not only permissive for transcription, but can override the requirement for the transcription factor at an inducible promoter.
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