title: SMARCAD1 Contributes to the Regulation of Naive Pluripotency by Interacting with Histone Citrullination.
abstract: 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.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Bharat
authors.initials: B
authors.lastname: Sridhar
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Chieh-Chun
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Darina
authors.initials: D
authors.lastname: McDee
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Sloofman
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Rivas-Astroza
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA.
authors.forename: Bhanu Prakash V L
authors.initials: BPVL
authors.lastname: Telugu
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Levasseur
authors.affiliation: Department of Ophthalmology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Liang
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Jing Crystal
authors.initials: JC
authors.lastname: Zhao
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Tetsuya S
authors.initials: TS
authors.lastname: Tanaka
authors.affiliation: Department of Genetics, Washington University at St. Louis, St. Louis, MO 63108, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Stormo
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: szhong@ucsd.edu.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D000076302:Citrullination; D004265:DNA Helicases; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D055785:Gene Knockdown Techniques; D016678:Genome; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D059467:Transcriptome / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D004265:DNA Helicases; C079429:Smarcad1 protein, mouse; D008239:Lysine
keywords: ChIP-seq; SMARCAD1; citrullination; histone modification; naive state; pluripotency; protein array; stem cells