1,721,051 research outputs found
Methylation status of Dnmt1 promoter depends on poly(ADP-ribosy)lation
Full text linkMacino, Giuseppe Bagni, Claudia Urbani, Andrea Piaggio, Giuli
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
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
Epigenetics: poly(ADP-ribosyl)ation of PARP-1 regulates genomic methylation pattern
No full textIn the postgenome era, attention is being focused on those epigenetic modifications that modulate chromatin structure to guarantee that information present on DNA is read correctly and at the most appropriate time to meet cellular requirements. Data reviewed show that along the chain of events that induce DNA methylation-dependent chromatin condensation/decondensation, a postsynthetic modification other than histone acetylation, phosphorylation, and methylation—namely poly(ADP-ribosyl)ation (PARylation)—participates in the establishment and maintenance of a genome methylation pattern. We hypothesize that the right nuclear balance between unmodified and PARylated poly(ADP-ribose) polymerase 1 (PARP-1), which depends on the dynamics of PARPs/PARG activity, is key to maintaining genomic methylation pattern. According to our data, decreased or increased levels of PARylated PARP-1 are responsible for diffuse hypermethylation or hypomethylation of DNA, respectively. In our model, polymers present on PARP-1 interact noncovalently with DNA methyltransferase 1 (Dnmt1), preventing its enzymatic activity. In the absence of PARylated PARP-1, Dnmt1 is free to methylate DNA; if, in contrast, high levels of PARylated PARP-1 persist, Dnmt1 will be stably inhibited, preventing DNA methylation
PARP1 orchestrates epigenetic events setting up chromatin domains
No full textEpigenetic events include reversible modifications of DNA and histone tails driving chromatin organization and thus transcription. The epigenetic regulation is a highly integrated process underlying the plasticity of the genomic information both in the context of complex physiological and pathological processes. The global regulatory aspects of epigenetic events are largely unknown. PARylation and PARP1 are recently emerging as multi-level regulatory effectors that modulate the topology of chromatin by orchestrating very different processes. This review focuses in particular on the role of PARP1 in epigenetics, trying to build a comprehensive perspective of its involvement in the regulation of epigenetic modifications of histones and DNA, contextualizing it in the global organization of chromatin domains in the nucleus
5mC-hydroxylase activity is influenced by the PARylation of TET1 enzyme
Full text link5-hydroxymethylcytosine is a new epigenetic modification deriving from the oxidation of 5-methylcytosine by the TET hydroxylase enzymes. DNA hydroxymethylation drives DNA demethylation events and is involved in the control of gene expression. Deregulation of TET enzymes causes developmental defects and is associated with pathological conditions such as cancer. Little information thus far is available on the regulation of TET activity by post-translational modifications. Here we show that TET1 protein is able to interact with PARP-1/ARTD1 enzyme and is target of both noncovalent and covalent PARylation. In particular, we have demonstrated that the noncovalent binding of ADP-ribose polymers with TET1 catalytic domain decreases TET1 hydroxylase activity while the covalent PARylation stimulates TET1 enzyme. In addition, TET1 activates PARP-1/ARTD1 independently of DNA breaks. Collectively, our results highlight a complex interplay between PARylation and TET1 which may be helpful in coordinating the multiple biological roles played by 5-hydroxymethylcytosine and TET proteins
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