1,721,116 research outputs found
Poly(ADP-ribosyl)ated H1 histone as a possible trans-acting factor involving in maintaining the unmethylated state of CpG islands
No full textInhibition of poly(ADP-ribosyl)ation induces DNA hypermethylation
No full textOrganizzato dall'Istituto Pasteur, Fondazione Cenci-Bolognett
PARP and epigenetic regulation
No full textIn the post-genome era attention is being focused on those epigenetic modifications which modulate chromatin structure to guarantee that information present on DNA is read correctly and at the most appropriate time in order to meet cellular requirements. In this chapter data are reviewed which show that along the chain of events that induce DNA methylation-dependent chromatin condensation, a post-synthetic modification other than histone acetylation, phosphorylation and methylation, namely poly(ADP-ribosyl)ation, participates in the establishment and maintenance of methylation-free regions of chromatin. In fact, several lines of in vitro and in vivo evidence have shown that poly(ADP-ribosyl)ation is involved in the control of DNA methylation pattern, protecting genomic DNA from full methylation. Molecular mechanism(s) that might underpin the correlation between inhibition of poly(ADP-ribose) polymerases and DNA hypermethylation will be discussed. Finally the hypothesis is posited that inhibition of the poly(ADP-ribosyl)ation process in the cell may be responsible for the anomalous hypermethylation of tumor suppressor gene promoters during tumorigenesis
Characterization of Nucleosome and Nucleosome-like Subpopulations Differently Involved in Gene Expression
No full textThe unmethylated state of CpG islands in mouse fibroblasts depends on the poly(ADP-ribosyl)ation process
No full textIn vivo and in vitro experiments carried out on L929 mouse fibroblasts suggested that the poly(ADP-ribosyl)ation process acts somehow as a protecting agent against full methylation of CpG dinucleotides in genomic DNA. Since CpG islands, which are found almost exclusively at the 5'-end of housekeeping genes, are rich in CpG dinucleotides, which are the target of mammalian DNA methyltransferase, we examined the possibility that the poly(ADP-ribosyl)ation reaction is involved in maintaining the unmethylated state of these DNA sequences. Experiments were conducted by two different strategies, using either methylation-dependent restriction enzymes on purified genomic DNA or a sequence-dependent restriction enzyme on an aliquot of the same DNA, previously modified by a bisulfite reaction. With the methylation-dependent restriction enzymes, it was observed that the 'HpaII tiny fragments' greatly decreased when the cells were preincubated with 3- aminobenzamide, a well known inhibitor of poly(ADP-ribose) polymerase. The other experimental approach allowed us to prove that, as a consequence of the inhibition of the poly(ADP-ribosyl)ation process, an anomalous methylation pattern could be evidenced in the CpG island of the promoter fragment of the Htf9 gene, amplified from DNA obtained from fibroblasts preincubated with 3- aminobenzamide. These data confirm the hypothesis that, at least for the Htf9 promoter region, an active poly(ADP-ribosyl)ation protects the unmethylated state of the CpG island
Inhibition of poly(ADP-ribosyl)ation introduces an anomalous methylation pattern in genomic DNA and in transfected plasmid
No full textCCCTC-Binding Factor Meets Poly(ADP-Ribose) Polymerase-1
No full textCCCTC-binding factor (CTCF) is a ubiquitous Zn-finger-containing protein with numerous recognized functions, including, but not limited to, gene activation and repression, enhancer-blocking, X-chromosome inactivation, and gene imprinting. It is believed that the protein performs such a variety of functions by interacting with an array of very diverse proteins. In addition, CTCF undergoes several post-translational modifications, including poly(ADP-ribosyl)ation. The PARylated form of CTCF has recently been implicated in two important functions: gene imprinting and control of ribosomal gene transcription. Here, we summarize and critically discuss the available data on the interplay between CTCF and poly(ADP-ribosyl)ation in these two processes. We consider the newly described phenomena in the broader context of PARP's activities, including the crucial role of protein PARylation in the regulation of the genome methylation pattern
Why is DNA methylation of Igf2 CpG island shore affected during ageing?
Full text linkComment on: Pirazzini C, Giuliani C, Bacalini MG, Boattini A, Capri M, Fontanesi E, Marasco E, Mantovani V, Pierini M, Pini E, Luiselli D, Franceschi C. Garagnani P. Space/Population and Time/Age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age. AGING: V4, N7
CTCF and its protein partners: divide and rule?
No full textCTCF is a ubiquitous transcription factor that is involved in numerous, seemingly unrelated functions. These functions include, but are not limited to, positive or negative regulation of transcription, enhancer-blocking activities at developmentally regulated gene clusters and at imprinted loci, and X-chromosome inactivation. Here, we review recent data acquired with state-of-the-art technologies that illuminate possible mechanisms behind the diversity of CTCF functions. CTCF interacts with numerous protein partners, including cohesin, nucleophosmin, PARP1, Yy1 and RNA polymerase II. We propose that CTCF interacts with one or two different partners according to the biological context, applying the Roman principle of governance, 'divide and rule' (divide et impera)
DNA methylation and chromatin structure: The puzzling CpG islands
Full text linkDNA methylation is the epigenetic modification,which introduces 5mC as fifth base onto DNA. As for the distribution of 5rnCs, it is well known that they distribute themselves in a non-random fashion in genomic DNA so that methylation pattern is characterized by the presence of methylated cytosines on the bulk of DNA while the unmethylated ones are mainly located within particular regions termed CpG islands. These regions represent about 1% of genomic DNA and are generally found in the promoter region Of housekeeping genes. Their unmethylated state, which is an essential condition for the correct expression of correlated genes, is paradoxical if one considers that these regions are termed CpG islands because they are particularly rich in this dinucleotide, which is the best substrate for enzymes involved in DNA methylation. Anomalous insertion of methyl groups in these regions generally leads to the lack of transcription of correlated genes. An interesting scientific problem is to clarify the mechanism(s) whereby CpG islands, which remain protected from methylation in normal cells, are susceptible to methylation in tumour cells. How the CpG moieties in CpG islands become vulnerable or resistant to the action of DNA methyltransferases and can thus lose or maintain their characteristic pattern of methylation is still an open question. Our aim is to gather some mechanisms regarding this intriguing enigma, which, despite all energy spent, still remains all unresolved puzzle. (C) 2004 Wiley-Liss, Inc
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