Epigenetic marks at BRCA1 and p53 coding sequences in early human embryogenesis.
In the vertebrate genome, methylation of deoxycytosine residues of CpGs dinucleotide has been associated with transcriptional silencing of genes, parental imprinting, X-inactivation and chromatin remodelling. In human somatic tissues, the 5' end of the BRCA1 CpG island is methylated, whereas this region is unmethylated in mature germ cells and early embryos. In gametes, as in somatic tissues, the CpG sites in the coding region are methylated. We took advantage of this bimodal distribution as a model to analyse the epigenetic reprogramming of coding regions during early human embryogenesis using the bisulphite-based genomic sequencing method. During preimplantation divisions, exon 11 of BRCA1 was slowly demethylated and retained approximately 30% of its methylated residues at the blastocyst stage. Moreover, the change in the distribution of methylated residues was not restricted to the BRCA1 gene, since for another gene, p53, a relatively high level of methylation (50%) of exon 4 was observed in blastocysts. Taken together, these data suggest that a significant part of the methylated residues of coding sequences might be conserved during preimplantation development.
Magdinier
Frédérique
F
Laboratoire de Génétique, UMR 5641 CNRS, Laboratoire de Biologie de la Reproduction et du Développement, UCBL1, 8 avenue Rockefeller and INSERM U453, Centre Leon Berard, 69373 Lyon Cedex 08, France.
D'Estaing
Sandrine Giscard
SG
Peinado
Claire
C
Demirci
Banu
B
Berthet
Cyril
C
Guérin
Jean Franciois
JF
Dante
Robert
R
D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D019398:Genes, BRCA1; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53