Histone H1 Poly[ADP]-Ribosylation Regulates the Chromatin Alterations Required for Learning Consolidation

Fontán‐Lozano, Ángela; Suárez-Pereira, Irene; Horrillo, Angélica; del-Pozo-Martín, Yaiza; Hmadcha, Abdelkrim; Carrión, Ángel Manuel

doi:10.1523/jneurosci.3010-10.2010

Cited by 68 publications

(64 citation statements)

References 62 publications

(84 reference statements)

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“…Nonetheless, it can be concluded that DMN induced changes in histone proteins by way of reducing their extents of poly ADPribosylation during the initiation stage of DMN induced carcinogenesis. The PAR of histone proteins observed in our study confirms the earlier report of histones being the major target of cellular PAR (Kma and Sharan, 2006;Fontan-Lozano et al, 2010;Redon et al, 2010), making histones the most preferred target proteins for PAR.…”

Section: Discussionsupporting

confidence: 92%

Dimethylnitrosamine-Induced Reduction in the Level of Poly-ADP-Ribosylation of Histone Proteins of Blood Lymphocytes - a Sensitive and Reliable Biomarker for Early Detection of Cancer

Kma

Sharan²

2014

Asian Pacific Journal of Cancer Prevention

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Poly-ADP-ribosylation (PAR) is a post-translational modification of mainly chromosomal proteins. It is known to be strongly involved in several molecular events, including nucleosome-remodelling and carcinogenesis. In this investigation, it was attempted to evaluate PAR level as a reliable biomarker for early detection of cancer in blood lymphocyte histones. PAR of isolated histone proteins was monitored in normal and dimethylnitrosamine (DMN)-exposed mice tissues using a novel ELISA-based immuno-probe assay developed in our laboratory. An inverse relationship was found between the level of PAR and period of DMN exposure in various histone proteins of blood lymphocytes and spleen cells. With the increase in the DMN exposure period, there was reduction in the PAR level of individual histones in both cases. It was also observed that the decrease in the level of PAR of histones resulted in progressive relaxation of genomic DNA, perhaps triggering activation of genes that are involved in initiation of transformation. The observed effect of carcinogen on the PAR of blood lymphocyte histones provided us with a handy tool for monitoring biochemical or physiological status of individuals exposed to carcinogens without obtaining biopsies of cancerous tissues, which involves several medical and ethical issues. Obtaining blood from any patient and separating blood lymphocytes are routine medical practices involving virtually no medical intervention, post-procedure medical care or trauma to a patient. Moreover, the immuno-probe assay is very simple, sensitive, reliable and cost-effective. Therefore, combined with the ease of preparation of blood lymphocytes and the simplicity of the technique, immuno-probe assay of PAR has the potential to be applied for mass screening of cancer. It appears to be a promising step in the ultimate goal of making cancer detection simple, sensitive and reliable in the near future.

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Section: Discussionsupporting

confidence: 92%

Dimethylnitrosamine-Induced Reduction in the Level of Poly-ADP-Ribosylation of Histone Proteins of Blood Lymphocytes - a Sensitive and Reliable Biomarker for Early Detection of Cancer

Kma

Sharan²

2014

Asian Pacific Journal of Cancer Prevention

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“…generate long branched chains of poly(ADP-ribose) (PAR) 6 , covalently attached to lysines on PARP1 itself 7 as well as chromatin-components such as histones [8][9][10] .…”

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confidence: 99%

The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks

Ali¹,

Timinszky²,

Arribas-Bosacoma³

et al. 2012

Nat Struct Mol Biol

213

188

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Poly(ADP-ribose) polymerase I (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. Upon activation at sites of DNA damage, PARP1 modifies itself and other proteins by covalent addition of long branched polymers of ADP-ribose, which in turn recruit downstream DNA repair and chromatin remodelling factors. PARP1 recognizes DNA damage through its N-terminal DNA-binding domain (DBD), which consists of a tandem repeat of an unusual zinc-finger (ZnF) domain. We have now determined the crystal structure of the human PARP1-DBD bound to a DNA break. Along with functional analysis of PARP1 recruitment to sites of DNA damage in vivo, the structure reveals a dimeric assembly whereby ZnF1 and ZnF2 domains from separate PARP1 molecules form a strand-break recognition module that helps activate PARP1 by facilitating its dimerization and consequent trans-automodification.Short-patch repair of DNA single-strand breaks is initiated by poly(ADP-ribose) polymerase-1 (PARP1) -a multi-domain enzyme activated by binding of its N-terminal DNA-binding domain (DBD) to DNA breaks [1][2][3][4][5] . Activated PARP1 utilises NAD + to Correspondence to: Andreas G. Ladurner; Laurence H. Pearl; Antony W. Oliver. AUTHOR CONTRIBUTIONS A.A.E.A. purified the protein, crystallized the complex and collected the X-ray diffraction data; G.T. designed and constructed the PARP1-EGFP constructs and performed the laser DNA damage experiments; M.K. performed the FRAP experiments; P.O.H. engineered the knockdown PARP1 cell line and the wild-type imaging reporter constructs, and performed the in vitro complementation assays; M.H. and R.A.-B. engineered and purified mutant PARP1 constructs; A.G.L. designed the study and analysed the data; L.H.P designed the study, analysed the data and wrote the paper; A.W.O. made the baculovirus constructs, designed the purification protocol, and solved and refined the crystal structure. All authors discussed the results and commented on the manuscript. We have now determined the crystal structure of the DNA-binding domain of PARP1 (PARP1-DBD) encompassing the first two zinc-finger (ZnF) domains, bound to a DNA break. In contrast with structural analysis of the separated domains 22 , we show that DNA binding by both zinc-finger domains is essential to damage recruitment in vivo, and that ZnF1 and ZnF2 domains from separate PARP1 molecules act as a functional unit to generate a dimeric binding module that specifically recognizes the single-strand / double-strand transition at a recessed DNA break. Mutational analysis in vitro and in cells demonstrates the functional requirement for zinc-finger dimerisation and reveals a mechanism for bringing two PARP1 molecules into close proximity at a DNA break as a prerequisite for transmodification. RESULTS Structure of the PARP1-DBD -DNA ComplexAn N-terminal segment of human PARP1 (residues 5-202) was expressed in insect cells and purified by column chromatography. Screening with a range of DNA molecules...

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“…Previously, it has been reported that PARP-1 and its PARylation activity are critical in neuronal viability as well as in learning and memory (16,17). PARylation induces a fast and transient decondensation of chromatin structure and enables the transcription needed to form long-term memory in Aplysia and mammals (18,19).…”

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confidence: 99%

“…PARylation induces a fast and transient decondensation of chromatin structure and enables the transcription needed to form long-term memory in Aplysia and mammals (18,19). It has been shown recently that PARylation is increased in the hippocampus after memory consolidation and long-term potentiation (LTP), whereas inhibition of PARylation blocked memory and LTP induction (17). Based on these findings, and on the role of other histone modifications in cocaine action, we sought to determine if PARP-1 and PAR are required for the maladaptive learning associated with addiction.…”

mentioning

confidence: 99%

Essential role of poly(ADP-ribosyl)ation in cocaine action

Scobie

Damez-Werno

Sun

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Many of the long-term effects of cocaine on the brain's reward circuitry have been shown to be mediated by alterations in gene expression. Several chromatin modifications, including histone acetylation and methylation, have been implicated in this regulation, but the effect of other histone modifications remains poorly understood. Poly(ADP-ribose) polymerase-1 (PARP-1), a ubiquitous and abundant nuclear protein, catalyzes the synthesis of a negatively charged polymer called poly(ADP-ribose) or PAR on histones and other substrate proteins and forms transcriptional regulatory complexes with several other chromatin proteins. Here, we identify an essential role for PARP-1 in cocaine-induced molecular, neural, and behavioral plasticity. Repeated cocaine administration, including self-administration, increased global levels of PARP-1 and its mark PAR in mouse nucleus accumbens (NAc), a key brain reward region. Using PARP-1 inhibitors and viral-mediated gene transfer, we established that PARP-1 induction in NAc mediates enhanced behavioral responses to cocaine, including increased self-administration of the drug. Using chromatin immunoprecipitation sequencing, we demonstrated a global, genome-wide enrichment of PARP-1 in NAc of cocaine-exposed mice and identified several PARP-1 target genes that could contribute to the lasting effects of cocaine. Specifically, we identified sidekick-1-important for synaptic connections during development-as a critical PARP-1 target gene involved in cocaine's behavioral effects as well as in its ability to induce dendritic spines on NAc neurons. These findings establish the involvement of PARP-1 and PARylation in the long-term actions of cocaine.histone PARylation | drug addiction | medium spiny neurons

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Histone H1 Poly[ADP]-Ribosylation Regulates the Chromatin Alterations Required for Learning Consolidation

Cited by 68 publications

References 62 publications

Dimethylnitrosamine-Induced Reduction in the Level of Poly-ADP-Ribosylation of Histone Proteins of Blood Lymphocytes - a Sensitive and Reliable Biomarker for Early Detection of Cancer

Dimethylnitrosamine-Induced Reduction in the Level of Poly-ADP-Ribosylation of Histone Proteins of Blood Lymphocytes - a Sensitive and Reliable Biomarker for Early Detection of Cancer

The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks

Essential role of poly(ADP-ribosyl)ation in cocaine action

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