Global DNA demethylation during mouse erythropoiesis in vivo
Department of Pediatrics; Department of Cancer Biology
Medical Subject Headings
Animals; CpG Islands; DNA Methylation; DNA Replication; Dinucleoside Phosphates; Embryo, Mammalian; Erythroblasts; Erythropoiesis; Gene Expression Regulation, Developmental; Genome; Liver; Locus Control Region; Long Interspersed Nucleotide Elements; Mice; S Phase; Sequence Analysis, DNA; Transcription, Genetic; beta-Globins
Hematology | Oncology | Pediatrics
In the mammalian genome, 5'-CpG-3' dinucleotides are frequently methylated, correlating with transcriptional silencing. Genome-wide demethylation is thought to occur only twice during development, in primordial germ cells and in the pre-implantation embryo. These demethylation events are followed by de novo methylation, setting up a pattern inherited throughout development and modified only at tissue-specific loci. We studied DNA methylation in differentiating mouse erythroblasts in vivo by using genomic-scale reduced representation bisulfite sequencing (RRBS). Demethylation at the erythroid-specific β-globin locus was coincident with global DNA demethylation at most genomic elements. Global demethylation was continuous throughout differentiation and required rapid DNA replication. Hence, DNA demethylation can occur globally during somatic cell differentiation, providing an experimental model for its study in development and disease.
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Citation: Science. 2011 Nov 11;334(6057):799-802. DOI: 10.1126/science.1207306. Link to article on publisher's website