Role of SmcHD1 in establishment of epigenetic states required for the maintenance of the X-inactivated state in mice
Yuki Sakakibara, Koji Nagao, Marnie Blewitt, Hiroyuki Sasaki, Chikashi Obuse, Takashi Sado
DEVELOPMENT | COMPANY BIOLOGISTS LTD | Published : 2018
X inactivation in mammals is regulated by epigenetic modifications. Functional deficiency of SmcHD1 has been shown to cause de-repression of X-inactivated genes in post-implantation female mouse embryos, suggesting a role of SmcHD1 in the maintenance of X inactivation. Here, we show that de-repression of X-inactivated genes accompanied a local reduction in the enrichment of H3K27me3 in mouse embryonic fibroblasts deficient for SmcHD1. Furthermore, many of these genes overlapped with those having a significantly lower enrichment of H3K27me3 at the blastocyst stage in wild type. Intriguingly, however, depletion of SmcHD1 did not compromise the X-inactivated state in immortalized female mouse e..View full abstract
Awarded by Ministry of Education, Culture, Sports, Science and Technology (MEXT)
Awarded by Japan Society for the Promotion of Science (JSPS)
Awarded by Australian National Health and Medical Research Council
This work was supported by Grants-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (16H01320 and 17H05606 to T.S.; 15H01462 and 17H06426 to K.N.) and a Grant-in-Aid for Scientific Research (A) and (C) from the Japan Society for the Promotion of Science (JSPS) (17H01588 to T.S.; 15K06942 to K.N.). M.B. was supported by a Bellberry-Viertel Senior Medical Research Fellowship, a grant from the Australian National Health and Medical Research Council (GNT1098290), and infrastructure funding via Victorian State Government Operational Infrastructure Support and Australian National Health and the Medical Research Council Research Institute Infrastructure Support Scheme.