Poly(ADP-ribose) Polymerase 1 (PARP1) Associates with E3 Ubiquitin-Protein Ligase UHRF1 and Modulates UHRF1 Biological Functions

Vos, Mike De; Ramy, Rosy El; Quénet, Delphine; Wolf, Patricia; Spada, Fabio; Magroun, Najat; Babbio, Federica; Schreiber, Valérie; Leonhardt, Heinrich; Bonapace, Ian Marc; Dantzer, Françoise

doi:10.1074/jbc.m113.527424

Cited by 40 publications

(36 citation statements)

References 58 publications

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“…The PARP1-EZH2 axis controls genes involved in cell differentiation; however, our data identify many additional pathways that are regulated by PARP activity, including genes that respond to different insults, such as DNA damage and oxidative stress, and genes involved in the ubiquitination pathway (27,48,49). Although works have shown that PARP is an important mediator in these pathways, our data extend the known contributions of PARP activity to include transcriptional regulation of multiple genes within these pathways, opening an interesting area of research.…”

Section: Discussionmentioning

confidence: 98%

“…While PARP activity is important for the transcriptional regulation of pathways common to all cell types, including the stress response (27) and the ubiquitination pathway (49), this study extends the relationship between PARP activity and cellular functions to include the regulation of B cells. For example, gene ontology analysis of our RNA-seq data showed that PARP inhibition affects genes involved in the Nur77 and nuclear factor of activated T cell signaling pathways, which are activated by B cell receptor stimulation (50,51).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2

Martin

Cesaroni

Denny

et al. 2015

Molecular and Cellular Biology

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2

Martin

Cesaroni

Denny

et al. 2015

Molecular and Cellular Biology

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“…The ubiquitin transferase, UHRF1, interacts with and recruits DNMT1 (Sharif et al 2007); thus, it could be repelled because it complexes with DNMT1. PARP1 can also be part of a complex with UHRF1 and DNMT1 (Sharif et al 2007), and it regulates UHRF1's interaction with DNMT1 by addition of poly(ADP-ribose) (De Vos et al 2014). In addition, PARP1 binds gene promoters and regulates transcription (Krishnakumar et al 2008).…”

Section: Resultsmentioning

confidence: 99%

Human proteins that interact with RNA/DNA hybrids

et al. 2018

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RNA/DNA hybrids form when RNA hybridizes with its template DNA generating a three-stranded structure known as the R-loop. Knowledge of how they form and resolve, as well as their functional roles, is limited. Here, by pull-down assays followed by mass spectrometry, we identified 803 proteins that bind to RNA/DNA hybrids. Because these proteins were identified using in vitro assays, we confirmed that they bind to R-loops in vivo. They include proteins that are involved in a variety of functions, including most steps of RNA processing. The proteins are enriched for K homology (KH) and helicase domains. Among them, more than 300 proteins preferred binding to hybrids than double-stranded DNA. These proteins serve as starting points for mechanistic studies to elucidate what RNA/DNA hybrids regulate and how they are regulated.

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“…Uhrf1 also possesses a RING finger domain, which has been linked to histone and protein ubiquitination and turnover (Citterio et al 2004;Liu et al 2013;Nishiyama et al 2013;Qin et al 2015). Moreover, Uhrf1 has also been involved in establishing and reorganizing heterochromatin sites (Papait et al 2008;De Vos et al 2014). In embryonic or skin stem cells, Uhrf1 is expressed during proliferation and downregulated upon differentiation (Sharif et al 2007;Sen et al 2010).…”

mentioning

confidence: 99%

Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration

et al. 2016

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In order to understand whether early epigenetic mechanisms instruct the long-term behavior of neural stem cells (NSCs) and their progeny, we examined Uhrf1 (ubiquitin-like PHD ring finger-1; also known as Np95), as it is highly expressed in NSCs of the developing brain and rapidly down-regulated upon differentiation. Conditional deletion of Uhrf1 in the developing cerebral cortex resulted in rather normal proliferation and neurogenesis but severe postnatal neurodegeneration. During development, deletion of Uhrf1 lead to global DNA hypomethylation with a strong activation of the intracisternal A particle (IAP) family of endogenous retroviral elements, accompanied by an increase in 5-hydroxymethylcytosine. Down-regulation of Tet enzymes rescued the IAP activation in Uhrf1 conditional knockout (cKO) cells, suggesting an antagonistic interplay between Uhrf1 and Tet on IAP regulation. As IAP up-regulation persists into postnatal stages in the Uhrf1 cKO mice, our data show the lack of means to repress IAPs in differentiating neurons that normally never express Uhrf1. The high load of viral proteins and other transcriptional deregulation ultimately led to postnatal neurodegeneration. Taken together, these data show that early developmental NSC factors can have long-term effects in neuronal differentiation and survival. Moreover, they highlight how specific the consequences of widespread changes in DNA methylation are for certain classes of retroviral elements. Neurogenesis is a complex process comprising several critical steps from proliferation of stem and progenitor cells to their differentiation and maturation into neurons. Each step of the neurogenic cascade is under tight transcriptional and post-transcriptional control and needs to be coordinated with the next differentiation step. Several transcription factors have been identified with key roles in specifying neurogenic fate in neural stem or progenitor cells, such as proneural factors Ascl1 and Ngn2, homeobox transcription factors Pax6 and Dlx, and many others (Schuurmans and Guillemot 2002;Wilkinson et al. 2013). These factors have early effects on neural stem cell (NSC) behavior and neurogenesis via transcriptional regulation. However, much less is known regarding whether and how mechanisms acting early in NSCs may exert effects only at later stages of neuronal differentiation or on postnatal gliogenesis. One of the key questions lies in unraveling the extent to which factors present at early developmental stages leave long-lasting traces on transcriptional regulation, affecting late stages of neuronal differentiation.One mechanism by which gene regulation is modulated is via epigenetic modifications, such as DNA methylation (Tyssowski et al. 2014). DNA methylation is carried out by the Dnmt group of methyltransferases: Dnmt1, Dnmt3a, and Dnmt3b. Dnmt3 enzymes are de novo methyltransferases, whereas Dnmt1 is largely involved in maintaining DNA methylation in somatic cycling cells. DNA methylation modulates the expression of

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Poly(ADP-ribose) Polymerase 1 (PARP1) Associates with E3 Ubiquitin-Protein Ligase UHRF1 and Modulates UHRF1 Biological Functions

Cited by 40 publications

References 58 publications

Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2

Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2

Human proteins that interact with RNA/DNA hybrids

Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration

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