1,721,034 research outputs found
Restriction Landmark Genome Scanning: a genome wide approach for assessing the methylation status of thousands of CpG islands
No full textInhibition of poly(ADP-ribosyl)ation introduces an anomalous methylation pattern in genomic DNA and in trasfected plasmid
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 textAnomalous methylation pattern of CpG islands as a consequence of the poly(ADP-ribosyl)ation block
No full textCorrelation between DNA methylation and poly(ADP-ribosyl)ation processes
No full textThe aim of this article is to show the close relationship between DNA methylation and poly(ADP-ribosyl)ation which are two important nuclear enzymatic mechanisms. An open question is to explain how some CpG dinucleotides, in particular those present into CpG islands, can maintain their unmethylated state in spite of the presence of active DNA methyltransferase in chromatin. This paper illustrates some data indicating that H1 histone is a possible trans-acting factor involved in protecting genomic DNA from full methylation and proposes that the somatic variant H1e, in its poly(ADP-ribosyl)ated isoform, is the protein capable of undertaking this role
Epigenetic plasticity of chromatin in embryonic and hematopoietic stem/progenitor cells: therapeutic potential of cell reprogramming
No full textDuring embryonic development and adult life, the plasticity and reversibility of modifications that affect the chromatin structure is important in the expression of genes involved in cell fate decisions and the maintenance of cell-differentiated state. Epigenetic changes in DNA and chromatin, which must occur to allow the accessibility of transcriptional factors at specific DNA-binding sites, are regarded as emerging major players for embryonic and hematopoietic stem cell (HSC) development and lineage differentiation. Epigenetic deregulation of gene expression, whether it be in conjunction with chromosomal alterations and gene mutations or not, is a newly recognized mechanism that leads to several diseases, including leukemia. The reversibility of epigenetic modifications makes DNA and chromatin changes attractive targets for therapeutic intervention. Here we review some of the epigenetic mechanisms that regulate gene expression in pluripotent embryonic and multipotent HSCs but may be deregulated in leukemia, and the clinical approaches designed to target the chromatin structure in leukemic cells
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