Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA;
Genome Res. 2014 May;24(5):809-20. doi: 10.1101/gr.163642.113. Epub 2014 Mar 25.
Polycomb-mediated chromatin repression modulates gene expression during development in metazoans. Binding of multiple sequence-specific factors at discrete Polycomb response elements (PREs) is thought to recruit repressive complexes that spread across an extended chromatin domain. To dissect the structure of PREs, we applied high-resolution mapping of nonhistone chromatin proteins in native chromatin of Drosophila cells. Analysis of occupied sites reveal interactions between transcription factors that stabilize Polycomb anchoring to DNA, and implicate the general transcription factor ADF1 as a novel PRE component. By comparing two Drosophila cell lines with differential chromatin states, we provide evidence that repression is accomplished by enhanced Polycomb recruitment both to PREs and to target promoters of repressed genes. These results suggest that the stability of multifactor complexes at promoters and regulatory elements is a crucial aspect of developmentally regulated gene expression.
多梳介导的染色质抑制在后生动物的发育过程中调节基因表达。多个序列特异性因子在离散的多梳反应元件（PREs）上的结合被认为招募了抑制复合物，这些复合物可以在扩展的染色质域上扩散。为了剖析 PREs 的结构，我们在果蝇细胞的天然染色质中应用了非组蛋白染色质蛋白的高分辨率作图。对占据位点的分析揭示了转录因子之间的相互作用，这些相互作用稳定了多梳蛋白与 DNA 的锚定，并暗示了一般转录因子 ADF1 是一个新的 PRE 组成部分。通过比较两个具有不同染色质状态的果蝇细胞系，我们提供了证据表明，抑制是通过增强多梳蛋白对 PRE 和受抑制基因的靶启动子的募集来实现的。这些结果表明，启动子和调控元件上多因子复合物的稳定性是发育调控基因表达的一个关键方面。
