Poly(ADP-ribose) polymerase 1 regulates nuclear reprogramming and promotes iPSC generation without c-Myc

Chiou, Shih Hwa; Jiang, Bo; Yu, Yung Luen; Chou, Shih Jie; Tsai, Ping-Hsing; Chang, Wei Chao; Chen, Liang Kung; Chen, Li Hsin; Chien, Yueh; Chiou, Guang Yuh

doi:10.1084/jem.20121044

Cited by 82 publications

(90 citation statements)

References 47 publications

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“…Our group and others have recently demonstrated that PARP1 is also involved in the efficient generation of iPSCs, which is probably due to PARP1‐dependent chromatin remodeling and epigenetic modulation 8, 11, 27. Here, we established strong physical and functional links between PARP1 and CHD1L and their roles in regulating the chromatin states of stemness genes.…”

Section: Discussionsupporting

confidence: 61%

“…The role of PARP1 in cell reprogramming has been demonstrated in recent studies, although the underlying mechanism of the PARP1‐driven stemness signature in promoting reprogramming efficiency remains unclear. CHD1L, a chromatin modulator that regulates nucleosome sliding, has been demonstrated to interact with PARP1 during DNA repair 22, 23, and our previous results demonstrated an interaction between CHD1L and PARP1 during cell reprogramming 27. Microarray analysis and WB results showed that the expression level of Parp1 parallels the expression of Chd1l , one of the ATP‐dependent chromatin‐remodeling enzymes active during the process of reprogramming, in reprogrammed cells at various stages of reprogramming (from Day 0.5 to Day 12; Fig.…”

Section: Resultsmentioning

confidence: 58%

“…Blocking of PARylation using a PARylation inhibitor has been used as an effective strategy for assessing the involvement of PARylation in cellular processes 8, 9, 27. To elucidate the role of PARylation status in the interaction between PARP1 and CHD1L, we performed an IP assay and WB to evaluate the catalytic activity of PARP1 in the pluripotent state and during early reprogramming.…”

Section: Resultsmentioning

confidence: 99%

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

Jiang¹,

Chen

et al. 2015

Stem Cells

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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

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Section: Discussionsupporting

confidence: 61%

Section: Resultsmentioning

confidence: 58%

Section: Resultsmentioning

confidence: 99%

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

Jiang¹,

Chen

et al. 2015

Stem Cells

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“…Poly(ADP-ribose) (PAR) is a reversible post-translational modification involved in multiple essential cellular processes including DNA damage, transcriptional control, and stem cell identity (Beneke, 2012; Chiou et al, 2013; Doege et al, 2012; Hassa and Hottiger, 2008; Ji and Tulin, 2010; Krishnakumar and Kraus, 2010a; Ogino et al, 2007; Tallis et al, 2013). Using NAD + as a substrate, poly(ADP-ribose) polymerases (PARPs) polymerize ADP-ribose subunits onto acceptor proteins, forming large, negatively charged polymers of varying length (Schreiber et al, 2006; Tan et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…PARP1, localized primarily to the nucleus, is the most abundant family member in humans (Vyas et al, 2013; Wang et al, 2012) and has been mainly examined in the context of base excision repair (Sousa et al, 2012). Recently PARP1 was implicated in other DNA repair pathways as well as in pathways outside of DNA repair such as transcription (Ji and Tulin, 2013; Krishnakumar and Kraus, 2010b) and stem cell identity (Chiou et al, 2013; Doege et al, 2012; Ogino et al, 2007). The details of its involvement in any of these pathways remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines

et al. 2014

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Summary Poly(ADP-ribose) polymerases (PARPs) catalyze poly(ADP-ribose) addition onto proteins, an important post-translational modification involved in transcription, DNA damage repair, and stem cell identity. Previous studies established the activation of PARP1 in response to DNA damage, but little is known about PARP1 regulation outside of DNA repair. We developed a new assay for measuring PARP activity in cell lysates, and found that the basal activity of PARP1 was highly variable across breast cancer cell lines, independent of DNA damage. Sucrose gradient fractionation demonstrated that PARP1 existed in at least three biochemically distinct states in both high and low activity lines. A newly discovered complex containing the NuA4 chromatin remodeling complex and PARP1 was responsible for high basal PARP1 activity, and NuA4 subunits were required for this activity. These findings present a new pathway for PARP1 activation and a direct link between PARP1 and chromatin remodeling outside of the DNA damage response.

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CHD1L promotes lineage reversion of hepatocellular carcinoma through opening chromatin for key developmental transcription factors

Liu

Chen

et al. 2016

Hepatology

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High-grade tumors with poor differentiation usually show phenotypic resemblance to their developmental ancestral cells. Cancer cells that gain lineage precursor cell properties usually hijack developmental signaling pathways to promote tumor malignant progression. However, the molecular mechanisms underlying this process remain unclear. In this study, the chromatin remodeler chromodomain-helicase-DNA-binding-protein 1-like (CHD1L) was found closely associated with liver development and hepatocellular carcinoma (HCC) tumor differentiation. Expression of CHD1L decreased during hepatocyte maturation and increased progressively from well-differentiated HCCs to poorly differentiated HCCs. Chromatin immunoprecipitation followed by high-throughput deep sequencing found that CHD1L could bind to the genomic sequences of genes related to development. Bioinformatics-aided network analysis indicated that CHD1L-binding targets might form networks associated with developmental transcription factor activation and histone modification. Overexpression of CHD1L conferred ancestral precursor-like properties of HCC cells both in vitro and in vivo. Inhibition of CHD1L reversed tumor differentiation and sensitized HCC cells to sorafenib treatment. Mechanism studies revealed that overexpression of CHD1L could maintain an active "open chromatin" configuration at promoter regions of estrogenrelated receptor-beta and transcription factor 4, both of which are important regulators of HCC self-renewal and differentiation. In addition, we found a significant correlation of CHD1L with developmental transcriptional factors and lineage differentiation markers in clinical HCC patients. Conclusion: Genomic amplification of chromatin remodeler CHD1L might drive dedifferentiation of HCC toward an ancestral lineage through opening chromatin for key developmental transcriptional factors; further inhibition of CHD1L might "downgrade" poorly differentiated HCCs and provide novel therapeutic strategies. (HEPATOLOGY 2016;63:1544-1559 I t has long been noted that various tumor cells usually show phenotypic resemblance to their ancestral precursor cells during normal organ development.(1) The gene expression signature and critical transcriptional factors governing lineage specification in development are reactivated in cancer cells and substantially contribute to malignant phenotypes such as tumor growth, metastasis, and resistance to

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Poly(ADP-ribose) polymerase 1 regulates nuclear reprogramming and promotes iPSC generation without c-Myc

Abstract: Parp1 can replace c-Myc to promote induced pluripotent stem cell (iPSC) generation.

Cited by 82 publications

References 47 publications

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

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

Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines

CHD1L promotes lineage reversion of hepatocellular carcinoma through opening chromatin for key developmental transcription factors

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