SMARCAD1 Contributes to the Regulation of Naive Pluripotency by Interacting with Histone Citrullination

Shu Xiao, Jia Lu, Bharat Sridhar, Xiaoyi Cao, Pengfei Yu, Tianyi Zhao, Chieh Chun Chen, Darina McDee, Laura Sloofman, Yang Wang, Marcelo Rivas-Astroza, Bhanu Prakash V.L. Telugu, Dana Levasseur, Kang Zhang, Han Liang, Jing Crystal Zhao, Tetsuya S. Tanaka, Gary Stormo, Sheng Zhong

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


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 ten histone modifications assayed by ChIP-seq, H3R26Cit exhibited the most extensive genomewide co-localization with SMARCAD1 binding. Increased Smarcad1 expression correlated with naive pluripotency in pre-implantation embryos. In the presence of LIF, Smarcad1 knockdown (KD) embryonic stem cells lost naive 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 naive pluripotency by interacting with H3R26Cit and suppressing heterochromatin formation.

Original languageEnglish
Pages (from-to)3117-3128
Number of pages12
JournalCell Reports
Issue number13
StatePublished - Mar 28 2017


  • ChIP-seq
  • citrullination
  • histone modification
  • naive state
  • pluripotency
  • protein array
  • stem cells


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