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PMID: 22076376 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Global DNA demethylation during mouse erythropoiesis in vivo.

Science (New York, N.Y.) ·Vol. 334 ·No. 6057 ·2011-11-11 ·Pages 799-802

Shearstone JR, Pop R, Bock C, Boyle P, Meissner A, Socolovsky M

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.

MeSH Terms
Animals CpG Islands DNA Methylation DNA Replication Dinucleoside Phosphates/metabolism Embryo, Mammalian Erythroblasts/metabolism Erythropoiesis Gene Expression Regulation, Developmental Genome Liver/embryology Locus Control Region Long Interspersed Nucleotide Elements Mice S Phase Sequence Analysis, DNA Transcription, Genetic beta-Globins/genetics
Chemicals
Dinucleoside Phosphates beta-Globins cytidylyl-3'-5'-guanosine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Shearstone Jeffrey R
Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Pop Ramona
Bock Christoph
Boyle Patrick
Meissner Alexander
Socolovsky Merav
References (31)
31 references, click to expand
  1. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication.
    Science. 1982 Oct 29;218(4571):474-5 PMID: 7123245
  2. Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency.
    Nature. 2010 Feb 25;463(7284):1101-5 PMID: 20098412
  3. Reprogramming towards pluripotency requires AID-dependent DNA demethylation.
    Nature. 2010 Feb 25;463(7284):1042-7 PMID: 20027182
  4. Diagnosis and characterization of acute erythroleukemia subsets by determining the percentages of myeloblasts and proerythroblasts in 69 cases.
    Am J Hematol. 2000 Sep;65(1):5-13 PMID: 10936857
  5. The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro.
    Blood. 1999 Jul 15;94(2):550-9 PMID: 10397722
  6. Epigenetic modifications in an imprinting cluster are controlled by a hierarchy of DMRs suggesting long-range chromatin interactions.
    Hum Mol Genet. 2003 Feb 1;12(3):295-305 PMID: 12554683
  7. Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI.
    Nucleic Acids Res. 1979;6(6):2125-32 PMID: 223125
  8. Analysis of gene expression data using BRB-ArrayTools.
    Cancer Inform. 2007 Feb 04;3:11-7 PMID: 19455231
  9. Intracellular hemoglobin-a specific marker for erythroid cells in paraffin sections. An immunoperoxidase study of normal, megaloblastic, and dysplastic erythropoiesis, including erythroleukemia and other myeloproliferative disorders.
    Am J Pathol. 1981 Mar;102(3):308-13 PMID: 7011040
  10. The gamma-globin gene promoter progressively demethylates as the hematopoietic stem progenitor cells differentiate along the erythroid lineage in baboon fetal liver and adult bone marrow.
    Exp Hematol. 2007 Jan;35(1):48-55 PMID: 17198873
  11. Enucleation of primitive erythroid cells generates a transient population of "pyrenocytes" in the mammalian fetus.
    Blood. 2008 Feb 15;111(4):2409-17 PMID: 18032705
  12. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation.
    Nature. 2007 Feb 8;445(7128):671-5 PMID: 17268471
  13. Rethinking how DNA methylation patterns are maintained.
    Nat Rev Genet. 2009 Nov;10(11):805-11 PMID: 19789556
  14. DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.
    Nat Genet. 2009 Nov;41(11):1207-15 PMID: 19801979
  15. Aphidicolin prevents mitotic cell division by interfering with the activity of DNA polymerase-alpha.
    Nature. 1978 Oct 5;275(5679):458-60 PMID: 692726
  16. Genome-scale DNA methylation maps of pluripotent and differentiated cells.
    Nature. 2008 Aug 7;454(7205):766-70 PMID: 18600261
  17. Negative autoregulation by FAS mediates robust fetal erythropoiesis.
    PLoS Biol. 2007 Oct;5(10):e252 PMID: 17896863
  18. Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: a direct role for Stat5 in Bcl-X(L) induction.
    Cell. 1999 Jul 23;98(2):181-91 PMID: 10428030
  19. The pCL vector system: rapid production of helper-free, high-titer, recombinant retroviruses.
    J Virol. 1996 Aug;70(8):5701-5 PMID: 8764092
  20. 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy.
    Oncogene. 2002 Aug 12;21(35):5483-95 PMID: 12154409
  21. Gene structure and transcription in mouse cells with extensively demethylated DNA.
    Mol Cell Biol. 1989 Mar;9(3):885-92 PMID: 2471061
  22. Histone modifications at human enhancers reflect global cell-type-specific gene expression.
    Nature. 2009 May 7;459(7243):108-12 PMID: 19295514
  23. A reversible arrest point in the late G1 phase of the mammalian cell cycle.
    Exp Cell Res. 1990 Feb;186(2):332-9 PMID: 2153561
  24. The sequence of a large L1Md element reveals a tandemly repeated 5' end and several features found in retrotransposons.
    Mol Cell Biol. 1986 Jan;6(1):168-82 PMID: 3023821
  25. LUMA (LUminometric Methylation Assay)--a high throughput method to the analysis of genomic DNA methylation.
    Exp Cell Res. 2006 Jul 1;312(11):1989-95 PMID: 16624287
  26. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation.
    Nat Genet. 2001 Jan;27(1):31-9 PMID: 11137995
  27. 5-Azacytidine increases fetal hemoglobin production in a patient with sickle cell disease.
    Prog Clin Biol Res. 1983;134:475-88 PMID: 6198661
  28. Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements.
    Mol Cell Biol. 2002 Jan;22(2):480-91 PMID: 11756544
  29. Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b.
    Mol Cell Biol. 2003 Aug;23(16):5594-605 PMID: 12897133
  30. BISMA--fast and accurate bisulfite sequencing data analysis of individual clones from unique and repetitive sequences.
    BMC Bioinformatics. 2010 May 06;11:230 PMID: 20459626
  31. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45.
    Cell. 2008 Dec 26;135(7):1201-12 PMID: 19109892
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1207306
Published
2011-11-11
Pages
799-802
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3230325
Subset
IM
Grants
NHLBI NIH HHS · R01 HL084168-04S1 · United States
NHLBI NIH HHS · R01 HL084168 · United States
NHLBI NIH HHS · R01 HL084168-05 · United States
NIDDK NIH HHS · DK32520 · United States
NHLBI NIH HHS · R01 HL084168-04 · United States
NHLBI NIH HHS · R01 HL084168-02 · United States
NHLBI NIH HHS · R01 HL084168-03 · United States
PHS HHS · T32-130807 · United States
NIDDK NIH HHS · P30 DK032520 · United States
Databases
GEO
GSE32214
External Links
PubMed source DOI: 10.1126/science.1207306 PMC Full Text View journal details
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