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Replication-coupled chromatin assembly generates a neuronal bilateral asymmetry in C. elegans

机译:复制耦合的染色质组装在秀丽隐杆线虫中产生神经元双侧不对称

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Although replication-coupled chromatin assembly is known to be important for the maintenance of patterns of gene expression through sequential cell divisions, the role of replication-coupled chromatin assembly in controlling cell differentiation during animal development remains largely unexplored. Here we report that the CAF-1 protein complex, an evolutionarily conserved histone chaperone that deposits histone H3-H4 proteins onto replicating DNA, is required to generate a bilateral asymmetry in the C. elegans nervous system. A mutation in 1 of 24 C. elegans histone H3 genes specifically eliminates this aspect of neuronal asymmetry by causing a defect in the formation of a histone H3-H4 tetramer and the consequent inhibition of CAF-1-mediated nucleosome formation. Our results reveal that replication-coupled nucleosome assembly is necessary to generate a bilateral asymmetry in C. elegans neuroanatomy and suggest that left-right asymmetric epigenetic regulation can establish bilateral asymmetry in the nervous system.
机译:尽管已知复制耦合的染色质组装对于通过连续的细胞分裂维持基因表达模式很重要,但是在动物发育过程中复制耦合的染色质组装在控制细胞分化中的作用仍未得到充分研究。在这里我们报告说,CAF-1蛋白复合物是一种进化上保守的组蛋白伴侣,可将组蛋白H3-H4蛋白沉积到复制的DNA上,是在秀丽隐杆线虫神经系统中产生双边不对称性所必需的。 24个秀丽隐杆线虫组蛋白H3基因中的1个突变通过在组蛋白H3-H4四聚体的形成中造成缺陷并因此抑制了CAF-1介导的核小体形成,从而消除了神经元不对称性的这一方面。我们的研究结果表明复制耦合核小体组装是必要的,以在秀丽隐杆线虫神经解剖中产生双侧不对称,并暗示左右不对称表观遗传调控可以在神经系统中建立双侧不对称。

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