Gene expression and Regulation program, The Wistar Institute, Philadelphia, PA, 19104, USA.
Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Nat Commun. 2020 May 6;11(1):2219. doi: 10.1038/s41467-020-15902-9.
Heterochromatin in the eukaryotic genome is rigorously controlled by the concerted action of protein factors and RNAs. Here, we investigate the RNA binding function of ATRX, a chromatin remodeler with roles in silencing of repetitive regions of the genome and in recruitment of the polycomb repressive complex 2 (PRC2). We identify ATRX RNA binding regions (RBRs) and discover that the major ATRX RBR lies within the N-terminal region of the protein, distinct from its PHD and helicase domains. Deletion of this ATRX RBR (ATRXΔRBR) compromises ATRX interactions with RNAs in vitro and in vivo and alters its chromatin binding properties. Genome-wide studies reveal that loss of RNA interactions results in a redistribution of ATRX on chromatin. Finally, our studies identify a role for ATRX-RNA interactions in regulating PRC2 localization to a subset of polycomb target genes.
真核基因组中的异染色质受到蛋白质因子和 RNA 的协同作用的严格控制。在这里，我们研究了 ATRX 的 RNA 结合功能，ATRX 是一种染色质重塑因子，在基因组重复区域的沉默和多梳抑制复合物 2 (PRC2) 的募集中发挥作用。我们确定了 ATRX 的 RNA 结合区域 (RBR)，并发现主要的 ATRX RBR 位于蛋白质的 N 端区域，与它的 PHD 和螺旋酶结构域不同。该 ATRX RBR（ATRXΔRBR）的缺失会损害 ATRX 与体外和体内 RNA 的相互作用，并改变其染色质结合特性。全基因组研究表明，RNA 相互作用的丧失导致 ATRX 在染色质上的重新分布。最后，我们的研究确定了 ATRX-RNA 相互作用在调节 PRC2 定位到一组多梳靶基因中的作用。
