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Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Rep 2017 ; 18 (13): 3117-28 Nephropedia Template TP
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SMARCAD1 contributes to regulation of naïve pluripotency by interacting with histone citrullination #MMPMID28355564
Xiao S; Lu J; Sridhar B; Cao X; Yu P; Zhao T; Chen CC; McDee D; Sloofman L; Wang Y; Rivas-Astroza M; Telugu BPV; Levasseur D; Zhang K; Liang H; Zhao JC; Tanaka TS; Stormo G; Zhong S
Cell Rep 2017[Mar]; 18 (13): 3117-28 PMID28355564show ga
Histone citrullination regulates diverse cellular processes. Here, we report that SMARCAD1 preferentially associates with H3 Arginine 26 citrullination (H3R26Cit) peptides present on arrays composed of 384 histone peptides harboring distinct post-transcriptional modifications. Among 10 histone modifications assayed by ChIP-seq, H3R26Cit exhibited the most extensive genomewide co-localization with SMARCAD1 binding. Increased Smarcad1 expression correlated with naïve pluripotency in pre-implantation embryos. In the presence of LIF, Smarcad1 knockdown (KD) embryonic stem cells lost naïve state phenotypes but remained pluripotent, as suggested by morphology, gene expression, histone modifications, alkaline phosphatase activity, energy metabolism, embryoid bodies, teratoma, and chimeras. The majority of H3R26Cit ChIP-seq peaks occupied by SMARCAD1 were associated with increased levels of H3K9me3 in Smarcad1 KD cells. Inhibition of H3Cit induced H3K9me3 at the overlapping regions of H3R26Cit peaks and SMARCAD1 peaks. These data suggest a model in which SMARCAD1 regulates naïve pluripotency by interacting with H3R26Cit and suppressing heterochromatin formation.