Histone variant H2A.Z regulates zygotic genome activation.
Histone variant H2A.Z regulates zygotic genome activation.
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DOI：
10.1038/s41467-021-27125-7
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发表时间：
2021-12-01
影响因子：
16.6
通讯作者：
Iovino N
中科院分区：
文献类型：
--
作者：
Ibarra-Morales D;Rauer M;Quarato P;Rabbani L;Zenk F;Schulte-Sasse M;Cardamone F;Gomez-Auli A;Cecere G;Iovino N
在胚胎发育过程中，基因组从转录静止状态转变为广泛活跃的状态，这一过程被称为合子基因组激活(ZGA)。在果蝇中，已知先锋因子塞尔达对发育进程是必不可少的；然而，它只调节ZGA处一小部分基因的激活。然而，数以千计的基因不需要塞尔达，这表明存在其他机制。通过在果蝇胚胎中进行Gro-SEQ、HIC和CHIP-SEQ，我们证明了高达65%的合子激活基因富集组蛋白变异体H_2A.Z。H_2A.Z富集组蛋白变异体H_2A.Z先于ZGA和RNA聚合酶II负载到染色质上。在体内，母系贡献的Domino，一种组蛋白伴侣和ATPase，减少了转录起始点的H2A.Z沉积，导致ZGA管家基因的全局下调，并损害了3D染色质结构的建立。我们推测，在ZGA过程中，通过染色质重组，H2A.Z对于转录程序的从头建立是必不可少的。在胚胎发育过程中，基因组在被称为合子基因组激活(ZGA)的过程中变得转录活跃；ZGA是如何启动的仍然是一个悬而未决的问题。在这里，作者展示了组蛋白变异H_2A.Z沉积在RNA聚合酶II与染色质结合之前，在ZGA之前。H2A.Z缺失会导致ZGA基因转录下调，并导致3D基因组结构的变化。
During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development; still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z. H2A.Z enrichment precedes ZGA and RNA Polymerase II loading onto chromatin. In vivo knockdown of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that H2A.Z is essential for the de novo establishment of transcriptional programs during ZGA via chromatin reorganization. During embryogenesis, the genome becomes transcriptionally active in a process known as zygotic genome activation (ZGA); how ZGA is initiated is still an open question. Here the authors show histone variant H2A.Z deposition precedes RNA polymerase II binding on chromatin, before ZGA. H2A.Z loss causes transcriptional downregulation of ZGA genes and leads to changes in the 3D genome organization.
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