Loss of PRC1 induces higher-order opening of Hox loci independently of transcription during Drosophila embryogenesis.

Loss of PRC1 induces higher-order opening of Hox loci independently of transcription during Drosophila embryogenesis.
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DOI:
10.1038/s41467-018-05945-4
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发表时间:
2018-09-25
影响因子:
16.6
通讯作者:
Cavalli G
Cavalli G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cheutin T;Cavalli G

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多梳蛋白是保守的染色质因子,可维持关键发育基因(尤其是 Hox 基因簇)在其表达域之外的沉默。 Polycomb 抑制复合物 1 (PRC1) 蛋白的耗尽通常会导致染色质解折叠以及异位转录。为了解开这两种现象,我们在这里分析了果蝇胚胎发生过程中 Hox 基因簇上两个 PRC1 蛋白 Polyhomeotic (Ph) 和 Polycomb (Pc) 的时间功能。我们发现Ph或Pc的缺失会影响Hox簇在异位Hox基因转录之前的高阶染色质折叠,证明PRC1在早期胚胎发生期间的主要功能是压缩其目标染色质。此外,Ph和Pc对Hox簇折叠的不同影响与在这两种突变体中观察到的异位Hox基因表达的差异相匹配。我们的数据表明 PRC1 通过折叠染色质结构域来维持基因沉默,并对基因调控施加结构层。 Polycomb 抑制复合物 1 (PRC1) 蛋白的丢失通常会导致染色质解折叠和异位转录。在这里,作者分析了果蝇胚胎发生过程中两种 PRC1 蛋白的时间功能,并提供了 PRC1 通过折叠染色质结构域维持基因沉默的证据。
Polycomb-group proteins are conserved chromatin factors that maintain the silencing of key developmental genes, notably the Hox gene clusters, outside of their expression domains. Depletion of Polycomb repressive complex 1 (PRC1) proteins typically results in chromatin unfolding, as well as ectopic transcription. To disentangle these two phenomena, here we analyze the temporal function of two PRC1 proteins, Polyhomeotic (Ph) and Polycomb (Pc), on Hox gene clusters during Drosophila embryogenesis. We show that the absence of Ph or Pc affects the higher-order chromatin folding of Hox clusters prior to ectopic Hox gene transcription, demonstrating that PRC1 primary function during early embryogenesis is to compact its target chromatin. Moreover, the differential effects of Ph and Pc on Hox cluster folding match the differences in ectopic Hox gene expression observed in these two mutants. Our data suggest that PRC1 maintains gene silencing by folding chromatin domains and impose architectural layer to gene regulation. Loss of Polycomb repressive complex 1 (PRC1) proteins usually results in both chromatin unfolding and ectopic transcription. Here, the authors analyze the temporal function of two PRC1 proteins during Drosophila embryogenesis and provide evidence that PRC1 maintains gene silencing by folding chromatin domains.
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期刊: HOX GENES: METHODS AND PROTOCOLS
影响因子: --
作者:
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