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首页> 外文期刊>Epigenetics & Chromatin >Fine-tuning of chromatin composition and Polycomb recruitment by two Mi2 homologues during C. elegans early embryonic development
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Fine-tuning of chromatin composition and Polycomb recruitment by two Mi2 homologues during C. elegans early embryonic development

机译：秀丽隐杆线虫早期胚胎发育过程中的两个Mi2同源物对染色质组成和Polycomb募集的微调

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Background The nucleosome remodeling and deacetylase complex promotes cell fate decisions throughout embryonic development. Its core enzymatic subunit, the SNF2-like ATPase and Helicase Mi2, is well conserved throughout the eukaryotic kingdom and can be found in multiple and highly homologous copies in all vertebrates and some invertebrates. However, the reasons for such duplications and their implications for embryonic development are unknown. Results Here we studied the two C. elegans Mi2 homologues, LET-418 and CHD-3, which displayed redundant activities during early embryonic development. At the transcriptional level, these two Mi2 homologues redundantly repressed the expression of a large gene population. We found that LET-418 physically accumulated at TSS-proximal regions on transcriptionally active genomic targets involved in growth and development. Moreover, LET-418 acted redundantly with CHD-3 to block H3K4me3 deposition at these genes. Our study also revealed that LET-418 was partially responsible for recruiting Polycomb to chromatin and for promoting H3K27me3 deposition. Surprisingly, CHD-3 displayed opposite activities on Polycomb, as it was capable of moderating its LET-418-dependent recruitment and restricted the amount of H3K27me3 on the studied target genes. Conclusion Although closely homologous, LET-418 and CHD-3 showed both redundant and opposite functions in modulating the chromatin environment at developmental target genes. We identified the interplay between LET-418 and CHD-3 to finely tune the levels of histone marks at developmental target genes. More than just repressors, Mi2-containing complexes appear as subtle modulators of gene expression throughout development. The study of such molecular variations in vertebrate Mi2 counterparts might provide crucial insights to our understanding of the epigenetic control of early development.
机译：背景技术核小体重塑和脱乙酰酶复合物可促进整个胚胎发育过程中的细胞命运决定。它的核心酶亚基，如SNF2样ATPase和Helicase Mi2，在整个真核生物王国中都保存完好，在所有脊椎动物和一些无脊椎动物中都可以发现多个高度同源的拷贝。但是，这种重复的原因及其对胚胎发育的影响尚不清楚。结果在这里，我们研究了两个秀丽隐杆线虫Mi2同源物LET-418和CHD-3，它们在早期胚胎发育过程中表现出多余的活性。在转录水平上，这两个Mi2同源物冗余地抑制了大基因群体的表达。我们发现LET-418物理积累在参与生长和发育的转录活性基因组靶标上的TSS近端区域。此外，LET-418与CHD-3重复发挥作用，以阻止H3K4me3在这些基因上的沉积。我们的研究还表明，LET-418对招募Polycomb染色质和促进H3K27me3沉积负有部分责任。出人意料的是，CHD-3在Polycomb上表现出相反的活性，因为它能够调节其LET-418依赖的募集并限制了所研究靶基因上的H3K27me3数量。结论尽管LET-418和CHD-3同源性很强，但它们在调节发育目标基因的染色质环境中却具有冗余和相反的功能。我们确定了LET-418和CHD-3之间的相互作用，以微调发育目标基因上组蛋白标记的水平。不仅限于阻遏物，含Mi2的复合物在整个发育过程中还表现为基因表达的细微调节剂。对脊椎动物Mi2对应物中此类分子变异的研究可能为我们对早期发育的表观遗传控制的理解提供重要的见识。

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