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

Cell Reports

Bhanu Prakash V.L. Telugu¹  Shu Xiao²  Tianyi Zhao²  Marcelo Rivas-Astroza²  Darina McDee²  Bharat Sridhar²  Xiaoyi Cao²  Pengfei Yu²  Jia Lu²  Sheng Zhong²  Han Liang³  Gary Stormo⁴  Dana Levasseur⁵  Kang Zhang⁶  Laura Sloofman⁷  Chieh-Chun Chen⁷  Tetsuya S. Tanaka⁷  Jing Crystal Zhao⁸  Yang Wang⁸ 

[1] Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA;Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA;Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;Department of Genetics, Washington University at St. Louis, St. Louis, MO 63108, USA;Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA;Department of Ophthalmology, University of California, San Diego, La Jolla, CA 92093, USA;Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA;

关键词: SMARCAD1;    histone modification;    citrullination;    stem cells;    naive state;    pluripotency;    ChIP-seq;    protein array;   

DOI  :  10.1016/j.celrep.2017.02.070

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown