Open AccessCHD1L Regulated PARP1 ‐Driven Pluripotency and Chromatin Remodeling During the Early‐Stage Cell Reprogramming
Author(s) -
Jiang BoHua,
Chen WeiYi,
Li HsinYang,
Chien Yueh,
Chang WeiChao,
Hsieh PeiChen,
Wu Ping,
Chen ChiehYu,
Song HuiYung,
Chien ChianShiu,
Sung YenJen,
Chiou ShihHwa
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2116
Subject(s) - reprogramming , chromatin , parp1 , biology , chromatin remodeling , microbiology and biotechnology , homeobox protein nanog , gene knockdown , embryonic stem cell , induced pluripotent stem cell , cell , genetics , dna , poly adp ribose polymerase , cell culture , polymerase , gene
A bstract 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. S tem C ells 2015;33:2961–2972