The Drosophila MLR COMPASS complex is essential for programming cis-regulatory information and maintaining epigenetic memory during development

The Drosophila MLR COMPASS complex is essential for programming cis-regulatory information and maintaining epigenetic memory during development
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果蝇 MLR COMPASS 复合体对于顺式调控信息编程和发育过程中维持表观遗传记忆至关重要

DOI:
10.1093/nar/gkaa082
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发表时间:
2020
影响因子:
14.9
通讯作者:
Dingwall, Andrew K
Dingwall, Andrew K
中科院分区:
生物学2区
文献类型:
--
作者:
Zraly, Claudia B;Zakkar, Abdul;Perez, John Hertenstein;Ng, Jeffrey;White, Kevin P;Slattery, Matthew;Dingwall, Andrew K

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MLR COMPASS复合物使H3K4单甲基化,H3K4用于表观遗传标记转录增强子,以在动物发育期间驱动适当的基因表达。果蝇MLR复合体的染色质富集分析揭示了与胚胎中启动子和增强子的动态关联,晚期富集偏向于活性和平衡增强子。含有染色质结合PHD指结构域的Cmi(也称为Lpt)亚基的RNAi消耗减弱了增强子功能,但出乎意料地导致在激素应答性增强子处于平衡状态的阶段期间不适当的增强子活化,揭示了取决于发育背景的增强子活化和抑制中涉及的关键表观遗传作用。Cmi对于标记活性增强子的稳健H3 K4单甲基化和H3 K27乙酰化是必需的,但对于MLR甲基转移酶Trr的染色质结合不是必需的。我们的数据揭示了MLR功能的两种可能的主要调控模式,即在早期胚胎发生中对增强子调试的贡献,以及在随后的发育阶段对增强子进行书签标记以实现快速转录再激活。
The MLR COMPASS complex monomethylates H3K4 that serves to epigenetically mark transcriptional enhancers to drive proper gene expression during animal development. Chromatin enrichment analyses of the Drosophila MLR complex reveals dynamic association with promoters and enhancers in embryos with late stage enrichments biased toward both active and poised enhancers. RNAi depletion of the Cmi (also known as Lpt) subunit that contains the chromatin binding PHD finger domains attenuates enhancer functions, but unexpectedly results in inappropriate enhancer activation during stages when hormone responsive enhancers are poised, revealing critical epigenetic roles involved in both the activation and repression of enhancers depending on developmental context. Cmi is necessary for robust H3K4 monomethylation and H3K27 acetylation that mark active enhancers, but not for the chromatin binding of Trr, the MLR methyltransferase. Our data reveal two likely major regulatory modes of MLR function, contributions to enhancer commissioning in early embryogenesis and bookmarking enhancers to enable rapid transcriptional re-activation at subsequent developmental stages.
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