Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02115, USA;
Genome Res. 2012 Jun;22(6):1015-25. doi: 10.1101/gr.133280.111. Epub 2012 Apr 16.
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.
转录因子顺式作用元件高度具有细胞类型特异性。染色质可及性、组蛋白修饰和核小体占有率都被发现对这些结合位置的定义起着作用。在这里，我们展示了激素诱导的 DNA 酶 I 超敏性变化（ΔDHS）在前列腺癌和乳腺癌细胞中分别高度预测了雄激素受体（AR）和雌激素受体 1（ESR1）的结合。虽然在受体结合之前的染色质结构和结合之后的核小体占有率在 ESR1 和 AR 之间存在显著差异，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 超敏性变化都有关。相比之下，虽然全局 ESR1 结合与核小体占有率变化无关，但 DNA 酶 I 超敏性动态也可预测 ESR1 顺式作用元件。这些发现表明，AR 和 ESR1 与染色质的相互作用具有不同的模式，而 DNA 酶 I 超敏性动态为预测细胞类型特异性顺式作用元件提供了一种通用方法。
