ATRX Partners with Cohesin and MeCP2 and Contributes to Developmental Silencing of Imprinted Genes in the Brain

摘要: Human developmental disorders caused by chromatin dysfunction often display overlapping clinical manifestations, such as cognitive deficits, but the underlying molecular links are poorly defined. Here, we show that ATRX, MeCP2, and cohesin, regulators implicated in ATR-X, RTT, CdLS syndromes, respectively, interact brain colocalize at H19 imprinting control region (ICR) with preferential binding on maternal allele. Importantly, ATRX loss of function alters enrichment CTCF, histone modifications ICR, without affecting DNA methylation paternal also affects MeCP2 occupancy within Gtl2/Dlk1 imprinted domain. Finally, interferes postnatal silencing gene along a larger network genes. We propose cooperate to silence subset genes mouse brain.