title: Global DNA demethylation during mouse erythropoiesis in vivo.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Shearstone
authors.forename: Ramona
authors.initials: R
authors.lastname: Pop
authors.forename: Christoph
authors.initials: C
authors.lastname: Bock
authors.forename: Patrick
authors.initials: P
authors.lastname: Boyle
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
authors.forename: Merav
authors.initials: M
authors.lastname: Socolovsky
mesh_terms: D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D004261:DNA Replication; D015226:Dinucleoside Phosphates / Q000378:metabolism; D004622:Embryo, Mammalian; D004900:Erythroblasts / Q000378:metabolism*; D004920:Erythropoiesis; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D008099:Liver / Q000196:embryology; D019901:Locus Control Region; D020084:Long Interspersed Nucleotide Elements; D051379:Mice; D016196:S Phase; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D055544:beta-Globins / Q000235:genetics
chemical_list: D015226:Dinucleoside Phosphates; D055544:beta-Globins; C015772:CpG dinucleotide
references.citation: Science. 1982 Oct 29;218(4571):474-5
references.pmid: 7123245
references.citation: Nature. 2010 Feb 25;463(7284):1101-5
references.pmid: 20098412
references.citation: Nature. 2010 Feb 25;463(7284):1042-7
references.pmid: 20027182
references.citation: Am J Hematol. 2000 Sep;65(1):5-13
references.pmid: 10936857
references.citation: Blood. 1999 Jul 15;94(2):550-9
references.pmid: 10397722
references.citation: Hum Mol Genet. 2003 Feb 1;12(3):295-305
references.pmid: 12554683
references.citation: Nucleic Acids Res. 1979;6(6):2125-32
references.pmid: 223125
references.citation: Cancer Inform. 2007 Feb 04;3:11-7
references.pmid: 19455231
references.citation: Am J Pathol. 1981 Mar;102(3):308-13
references.pmid: 7011040
references.citation: Exp Hematol. 2007 Jan;35(1):48-55
references.pmid: 17198873
references.citation: Blood. 2008 Feb 15;111(4):2409-17
references.pmid: 18032705
references.citation: Nature. 2007 Feb 8;445(7128):671-5
references.pmid: 17268471
references.citation: Nat Rev Genet. 2009 Nov;10(11):805-11
references.pmid: 19789556
references.citation: Nat Genet. 2009 Nov;41(11):1207-15
references.pmid: 19801979
references.citation: Nature. 1978 Oct 5;275(5679):458-60
references.pmid: 692726
references.citation: Nature. 2008 Aug 7;454(7205):766-70
references.pmid: 18600261
references.citation: PLoS Biol. 2007 Oct;5(10):e252
references.pmid: 17896863
references.citation: Cell. 1999 Jul 23;98(2):181-91
references.pmid: 10428030
references.citation: J Virol. 1996 Aug;70(8):5701-5
references.pmid: 8764092
references.citation: Oncogene. 2002 Aug 12;21(35):5483-95
references.pmid: 12154409
references.citation: Mol Cell Biol. 1989 Mar;9(3):885-92
references.pmid: 2471061
references.citation: Nature. 2009 May 7;459(7243):108-12
references.pmid: 19295514
references.citation: Exp Cell Res. 1990 Feb;186(2):332-9
references.pmid: 2153561
references.citation: Mol Cell Biol. 1986 Jan;6(1):168-82
references.pmid: 3023821
references.citation: Exp Cell Res. 2006 Jul 1;312(11):1989-95
references.pmid: 16624287
references.citation: Nat Genet. 2001 Jan;27(1):31-9
references.pmid: 11137995
references.citation: Prog Clin Biol Res. 1983;134:475-88
references.pmid: 6198661
references.citation: Mol Cell Biol. 2002 Jan;22(2):480-91
references.pmid: 11756544
references.citation: Mol Cell Biol. 2003 Aug;23(16):5594-605
references.pmid: 12897133
references.citation: BMC Bioinformatics. 2010 May 06;11:230
references.pmid: 20459626
references.citation: Cell. 2008 Dec 26;135(7):1201-12
references.pmid: 19109892