The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo.
The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo.
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DOI：
10.1242/dev.131961
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发表时间：
2016-04-15
期刊：
影响因子：
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通讯作者：
Zernicka-Goetz M
中科院分区：
文献类型：
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作者：
Panamarova M;Cox A;Wicher KB;Butler R;Bulgakova N;Jeon S;Rosen B;Seong RH;Skarnes W;Crabtree G;Zernicka-Goetz M
基因表达的动态控制对于全能受精卵发育成具有明确细胞谱系的胚胎至关重要。负责细胞规范的基因对转录机制的可及性取决于染色质重塑复合体，如SWI-SNF(BAF)复合体。然而，BAF复合体在小鼠早期发育中的作用尚不清楚。在这里，我们证明了BAF155，一个主要的BAF复合体亚基，在体内调节BAF复合体的组装，并调节小鼠囊胚的谱系特征。我们发现，BAF155与其他BAF复合亚单位的关联在植入前刚刚在胚胎外谱系中变得丰富。这种丰富归因于与胚胎谱系相比，BAF155在胚胎外的迁移率降低。BAF155的下调导致多能标记Nanog的表达增加，而BAF155的上调则导致分化标记的上调。最后，我们发现精氨酸甲基转移酶CARM1甲基化BAF155，这对BAF复合体在谱系之间的组装和多能性标记的表达产生了不同的影响。总之，我们的结果表明，通过调节谱系规范，BAF依赖的染色质重构在小鼠发育中扮演了一个新的角色。摘要：在植入前，BAF155与其他BAF复合体亚基的相关性在胚胎外谱系中丰富，而BAF155水平的变化调节早期发育标志物的表达。
Dynamic control of gene expression is essential for the development of a totipotent zygote into an embryo with defined cell lineages. The accessibility of genes responsible for cell specification to transcriptional machinery is dependent on chromatin remodelling complexes such as the SWI\SNF (BAF) complex. However, the role of the BAF complex in early mouse development has remained unclear. Here, we demonstrate that BAF155, a major BAF complex subunit, regulates the assembly of the BAF complex in vivo and regulates lineage specification of the mouse blastocyst. We find that associations of BAF155 with other BAF complex subunits become enriched in extra-embryonic lineages just prior to implantation. This enrichment is attributed to decreased mobility of BAF155 in extra-embryonic compared with embryonic lineages. Downregulation of BAF155 leads to increased expression of the pluripotency marker Nanog and its ectopic expression in extra-embryonic lineages, whereas upregulation of BAF155 leads to the upregulation of differentiation markers. Finally, we show that the arginine methyltransferase CARM1 methylates BAF155, which differentially influences assembly of the BAF complex between the lineages and the expression of pluripotency markers. Together, our results indicate a novel role of BAF-dependent chromatin remodelling in mouse development via regulation of lineage specification. Summary: Associations of BAF155 with other BAF complex subunits are enriched in extra-embryonic lineages prior to implantation, while changes in BAF155 levels modulate the expression of early developmental markers.