Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression.
Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression.
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DOI：
10.1101/gad.14.7.804
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发表时间：
2000-04
影响因子：
10.5
通讯作者：
Yasuhiko Takahashi;Joseph B. Rayman;B. Dynlacht
中科院分区：
文献类型：
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作者：
Yasuhiko Takahashi;Joseph B. Rayman;B. Dynlacht
在哺乳动物细胞周期进程中，E2F转录因子在及时激活基因表达方面起着关键作用，而pRB和相关蛋白部分通过阻断E2F的作用来控制细胞生长。为了确定生理上重要的e2f响应启动子，并研究它们在体内的占用和组蛋白乙酰化状态，我们在同步的活细胞中采用了交联方法。我们发现，当细胞从静止状态进入G(1)期和S期时，募集到这些启动子的E2F和prb相关多肽的模式以一种惊人的动态方式发生变化：静止细胞中每个启动子的抑制与E2F-4和p130的募集以及低水平的组蛋白乙酰化有关，但在G(1)晚期，这些蛋白质大部分被E2F-1和E2F-3所取代，与组蛋白H3和H4的乙酰化和基因激活相一致。这些发现表明，E2F应答基因的抑制和激活可能是通过不同的E2F异源二聚体发生的，这些异源二聚体指导了能够对核心组蛋白进行去乙酰化和乙酰化的酶的顺序募集。
The E2F transcription factor plays a pivotal role in the timely activation of gene expression during mammalian cell cycle progression, whereas pRB and related proteins control cell growth in part through the ability to block the action of E2F. To identify physiologically important E2F-responsive promoters and to study their occupancy and histone acetylation state in vivo, we have taken advantage of a cross-linking approach in synchronized, living cells. We find that the pattern of E2F and pRB-related polypeptides recruited to these promoters changes in a strikingly dynamic fashion as cells progress from quiescence into G(1) and S phase: Repression of each promoter in quiescent cells is associated with recruitment of E2F-4 and p130 and low levels of histone acetylation, but by late G(1), these proteins are replaced largely by E2F-1 and E2F-3, in concert with acetylation of histones H3 and H4 and gene activation. These findings suggest that repression and activation of E2F-responsive genes may occur through distinct E2F heterodimers that direct the sequential recruitment of enzymes able to deacetylate and then acetylate core histones.