title: CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the Early-Stage Cell Reprogramming.
abstract: PARP1 and poly(ADP-ribosyl)ation (PARylation) have been shown to be essential for the initial steps of cellular reprogramming. However, the mechanism underlying PARP1/PARylation-regulated activation of pluripotency loci remains undetermined. Here, we demonstrate that CHD1L, a DNA helicase, possesses chromatin remodeling activity and interacts with PARP1/PARylation in regulating pluripotency during reprogramming. We found that this interaction is mediated through the interplay of the CHD1L macro-domain and the PAR moiety of PARylated-PARP1. Chromatin immunoprecipitation assays demonstrated the co-occupancy of CHD1L and PARP1 at Pou5f1, Nanog, and Esrrb pluripotency loci. Knockdown of CHD1L significantly blocked the binding activity of PARP1 at pluripotency loci and inhibited the efficiency of PARP1-driven reprogramming. Notably, we found that CHD1L-promoted reprogramming requires both a PARP1-interacting domain and DNA helicase activity, partly contributing to the chromatin-remodeling states of pluripotency loci. Taken together, these results identify CHD1L as a key chromatin remodeler involved in PARP1/PARylation-regulated early-stage reprogramming and pluripotency in stem cells.
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Bo-Hua
authors.initials: BH
authors.lastname: Jiang
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.|VGH-YM Genomic/Cancer Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hsin-Yang
authors.initials: HY
authors.lastname: Li
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yueh
authors.initials: Y
authors.lastname: Chien
authors.affiliation: Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan.|Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Hsieh
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.|VGH-YM Genomic/Cancer Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hui-Yung
authors.initials: HY
authors.lastname: Song
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chian-Shiu
authors.initials: CS
authors.lastname: Chien
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yen-Jen
authors.initials: YJ
authors.lastname: Sung
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004265:DNA Helicases / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D039904:Pluripotent Stem Cells; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000096:biosynthesis
chemical_list: D004268:DNA-Binding Proteins; C098925:Esrrb protein, mouse; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011960:Receptors, Estrogen; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D004265:DNA Helicases; C546393:Chd1l protein, mouse
keywords: CHD1L; Chromatin remodeling; PARP1; PARylation; Reprogramming