Differential DNase I hypersensitivity reveals factor-dependent chromatin dynamics.

Differential DNase I hypersensitivity reveals factor-dependent chromatin dynamics.
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DOI:
10.1101/gr.133280.111
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发表时间:
2012-06
期刊:
影响因子:
7
通讯作者:
Liu XS
Liu XS
中科院分区:
生物学1区
文献类型:
--
作者:
He HH;Meyer CA;Chen MW;Jordan VC;Brown M;Liu XS

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转录因子顺反子是高度细胞类型特异性的。染色质可及性、组蛋白修饰和核小体占据都被发现在定义这些结合位置中起作用。在这里,我们表明,在前列腺癌和乳腺癌细胞中,雄激素受体(AR)和雌激素受体1(ESR1)的结合,分别高度预测由腺苷酸诱导的DNA酶I超敏反应的变化(ΔDHS)。虽然ESR1和AR在受体结合前的染色质结构和结合后的核小体占有率有显著差异,但ΔDHS对两者都具有高度预测性。AR结合与局部核小体占有率和DNA酶I超敏性的变化相关。相反,虽然整体ESR1结合与核小体占有率的变化无关,但DNA酶I超敏动力学也可预测ESR1顺式组。这些研究结果表明,AR和ESR1有不同的模式与染色质的相互作用,DNase I超敏动力学提供了一个通用的方法来预测细胞类型特异性顺反。
Transcription factor cistromes are highly cell-type specific. Chromatin accessibility, histone modifications, and nucleosome occupancy have all been found to play a role in defining these binding locations. Here, we show that hormone-induced DNase I hypersensitivity changes (ΔDHS) are highly predictive of androgen receptor (AR) and estrogen receptor 1 (ESR1) binding in prostate cancer and breast cancer cells, respectively. While chromatin structure prior to receptor binding and nucleosome occupancy after binding are strikingly different for ESR1 and AR, ΔDHS is highly predictive for both. AR binding is associated with changes in both local nucleosome occupancy and DNase I hypersensitivity. In contrast, while global ESR1 binding is unrelated to changes in nucleosome occupancy, DNase I hypersensitivity dynamics are also predictive of the ESR1 cistrome. These findings suggest that AR and ESR1 have distinct modes of interaction with chromatin and that DNase I hypersensitivity dynamics provides a general approach for predicting cell-type specific cistromes.
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