PMID- 28355564 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20200502 IS - 2211-1247 (Electronic) VI - 18 IP - 13 DP - 2017 Mar 28 TI - SMARCAD1 Contributes to the Regulation of Naive Pluripotency by Interacting with Histone Citrullination. PG - 3117-3128 LID - S2211-1247(17)30288-7 [pii] LID - 10.1016/j.celrep.2017.02.070 [doi] AB - 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. CI - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Xiao, Shu AU - Xiao S AD - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. FAU - Lu, Jia AU - Lu J AD - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. FAU - Sridhar, Bharat AU - Sridhar B AD - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. FAU - Cao, Xiaoyi AU - Cao X AD - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. FAU - Yu, Pengfei AU - Yu P AD - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. FAU - Zhao, Tianyi AU - Zhao T AD - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. FAU - Chen, Chieh-Chun AU - Chen CC AD - Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. FAU - McDee, Darina AU - McDee D AD - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. FAU - Sloofman, Laura AU - Sloofman L AD - Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. FAU - Wang, Yang AU - Wang Y AD - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Rivas-Astroza, Marcelo AU - Rivas-Astroza M AD - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. FAU - Telugu, Bhanu Prakash V L AU - Telugu BPVL AD - Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA. FAU - Levasseur, Dana AU - Levasseur D AD - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. FAU - Zhang, Kang AU - Zhang K AD - Department of Ophthalmology, University of California, San Diego, La Jolla, CA 92093, USA. FAU - Liang, Han AU - Liang H AD - Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Zhao, Jing Crystal AU - Zhao JC AD - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Tanaka, Tetsuya S AU - Tanaka TS AD - Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. FAU - Stormo, Gary AU - Stormo G AD - Department of Genetics, Washington University at St. Louis, St. Louis, MO 63108, USA. FAU - Zhong, Sheng AU - Zhong S AD - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: szhong@ucsd.edu. LA - eng GR - R01 EY025090/EY/NEI NIH HHS/United States GR - DP1 HD087990/HD/NICHD NIH HHS/United States GR - DP2 OD007417/OD/NIH HHS/United States GR - R01 GM110090/GM/NIGMS NIH HHS/United States GR - R01 HG000249/HG/NHGRI NIH HHS/United States GR - R01 HG008135/HG/NHGRI NIH HHS/United States GR - R01 CA217642/CA/NCI NIH HHS/United States PT - Journal Article PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 RN - 0 (Chromatin) RN - 0 (Histones) RN - 0 (Nuclear Proteins) RN - EC 3.6.4.- (DNA Helicases) RN - EC 3.6.4.- (Smarcad1 protein, mouse) RN - K3Z4F929H6 (Lysine) SB - IM MH - Animals MH - Base Sequence MH - Binding Sites MH - Cells, Cultured MH - Chromatin/metabolism MH - *Citrullination MH - DNA Helicases MH - Embryo, Mammalian/metabolism MH - Embryonic Development MH - Embryonic Stem Cells/metabolism MH - Epigenesis, Genetic MH - Female MH - Gene Knockdown Techniques MH - Genome MH - Histones/*metabolism MH - Lysine/metabolism MH - Male MH - Methylation MH - Mice MH - Nuclear Proteins/*metabolism MH - Phenotype MH - Pluripotent Stem Cells/*metabolism MH - Protein Binding MH - Protein Processing, Post-Translational MH - Transcriptome/genetics PMC - PMC5466819 MID - NIHMS856895 OTO - NOTNLM OT - ChIP-seq OT - SMARCAD1 OT - citrullination OT - histone modification OT - naive state OT - pluripotency OT - protein array OT - stem cells EDAT- 2017/03/30 06:00 MHDA- 2017/11/29 06:00 PMCR- 2017/06/10 CRDT- 2017/03/30 06:00 PHST- 2015/04/03 00:00 [received] PHST- 2017/02/08 00:00 [revised] PHST- 2017/02/23 00:00 [accepted] PHST- 2017/03/30 06:00 [entrez] PHST- 2017/03/30 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/06/10 00:00 [pmc-release] AID - S2211-1247(17)30288-7 [pii] AID - 10.1016/j.celrep.2017.02.070 [doi] PST - ppublish SO - Cell Rep. 2017 Mar 28;18(13):3117-3128. doi: 10.1016/j.celrep.2017.02.070.