CHD1L Regulated PARP1‐Driven Pluripotency and Chromatin Remodeling During the Early‐Stage Cell Reprogramming

• Published in: Stem cells (Dayton, Ohio) Vol. 33; no. 10; pp. 2961 - 2972
• Main Authors: Jiang, Bo‐Hua, Chen, Wei‐Yi, Li, Hsin‐Yang, Chien, Yueh, Chang, Wei‐Chao, Hsieh, Pei‐Chen, Wu, Ping, Chen, Chieh‐Yu, Song, Hui‐Yung, Chien, Chian‐Shiu, Sung, Yen‐Jen, Chiou, Shih‐Hwa
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.10.2015; John Wiley and Sons Inc
• Subjects: Animals; Cell Differentiation - genetics; Cellular Reprogramming - genetics; CHD1L; Chromatin; Chromatin Assembly and Disassembly - genetics; Chromatin remodeling; DNA Helicases - biosynthesis; DNA Helicases - genetics; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Embryonic Stem Cells/Induced Pluripotent Stem Cells; Gene Knockdown Techniques; Homeodomain Proteins - biosynthesis; Mice; Nanog Homeobox Protein; Octamer Transcription Factor-3 - biosynthesis; PARP1; PARylation; Pluripotent Stem Cells; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - biosynthesis; Poly(ADP-ribose) Polymerases - genetics; Receptors, Estrogen - biosynthesis; Reprogramming; Stem cells; Reprogramming; CHD1L; PARP1; Chromatin remodeling; PARylation
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.2116

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. Stem Cells 2015;33:2961–2972 • • •