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DRIAM 复合物拮抗 WDR5A 以调节组蛋白 H3K4me2/3 沉积,从而抑制基因组的一部分。

The DREAM complex antagonizes WDR5A to modulate histone H3K4me2/3 deposition for a subset of genome repression.

机构信息

State Key Laboratory of Protein and Plant Gene Research, School of Advanced Agricultural Sciences and School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.

State Key Laboratory of Protein and Plant Gene Research, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.

出版信息

Proc Natl Acad Sci U S A. 2022 Jul 5;119(27):e2206075119. doi: 10.1073/pnas.2206075119. Epub 2022 Jun 27.

Abstract

The master transcriptional repressor DREAM (dimerization partner, RB-like, E2F and multivulval class B) complex regulates the cell cycle in eukaryotes, but much remains unknown about how it transmits repressive signals on chromatin to the primary transcriptional machinery (e.g., RNA polymerase II [Pol II]). Through a forward genetic screen, we identified BTE1 (barrier of transcription elongation 1), a plant-specific component of the DREAM complex. The subsequent characterization demonstrated that DREAM complex containing BTE1 antagonizes the activity of Complex Proteins Associated with Set1 (COMPASS)-like complex to repress H3K4me3 occupancy and inhibits Pol II elongation at DREAM target genes. We showed that BTE1 is recruited to chromatin at the promoter-proximal regions of target genes by E2F transcription factors. DREAM target genes exhibit characteristic enrichment of H2A.Z and H3K4me2 modification on chromatin. We further showed that BTE1 directly interacts with WDR5A, a core component of COMPASS-like complex, repressing WDR5A chromatin binding and the elongation of transcription on DREAM target genes. H3K4me3 is known to correlate with the Pol II transcription activation and promotes efficient elongation. Thus, our study illustrates a transcriptional repression mechanism by which the DREAM complex dampens H3K4me3 deposition at a set of genes through its interaction with WDR5A.

摘要

主转录阻遏物 DREAM(二聚体伴侣、RB 样、E2F 和多育区 B)复合物在真核生物中调节细胞周期,但关于它如何将抑制信号从染色质传递到主要转录机制(例如 RNA 聚合酶 II [Pol II]),仍有许多未知之处。通过正向遗传筛选,我们鉴定了 BTE1(转录延伸障碍 1),它是 DREAM 复合物的植物特异性成分。随后的表征表明,含有 BTE1 的 DREAM 复合物拮抗了与 Set1 相关的复合物(COMPASS 样复合物)的活性,以抑制 H3K4me3 占据并抑制 DREAM 靶基因上的 Pol II 延伸。我们表明,E2F 转录因子将 BTE1 募集到靶基因启动子近端区域的染色质上。DREAM 靶基因在染色质上表现出特征性的 H2A.Z 和 H3K4me2 修饰富集。我们进一步表明,BTE1 直接与 WDR5A(COMPASS 样复合物的核心组成部分)相互作用,抑制 WDR5A 染色质结合和 DREAM 靶基因上的转录延伸。H3K4me3 已知与 Pol II 转录激活相关,并促进有效的延伸。因此,我们的研究说明了一种转录抑制机制,即 DREAM 复合物通过与 WDR5A 相互作用,在一组基因中抑制 H3K4me3 的沉积。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd8/9271193/eadd61db898e/pnas.2206075119fig01.jpg

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