PMID- 19829295
OWN - NLM
STAT- MEDLINE
DCOM- 20091130
LR  - 20240104
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 462
IP  - 7271
DP  - 2009 Nov 19
TI  - Human DNA methylomes at base resolution show widespread epigenomic differences.
PG  - 315-22
LID - 10.1038/nature08514 [doi]
AB  - DNA cytosine methylation is a central epigenetic modification that has essential 
      roles in cellular processes including genome regulation, development and disease. 
      Here we present the first genome-wide, single-base-resolution maps of methylated 
      cytosines in a mammalian genome, from both human embryonic stem cells and fetal 
      fibroblasts, along with comparative analysis of messenger RNA and small RNA 
      components of the transcriptome, several histone modifications, and sites of 
      DNA-protein interaction for several key regulatory factors. Widespread 
      differences were identified in the composition and patterning of cytosine 
      methylation between the two genomes. Nearly one-quarter of all methylation 
      identified in embryonic stem cells was in a non-CG context, suggesting that 
      embryonic stem cells may use different methylation mechanisms to affect gene 
      regulation. Methylation in non-CG contexts showed enrichment in gene bodies and 
      depletion in protein binding sites and enhancers. Non-CG methylation disappeared 
      upon induced differentiation of the embryonic stem cells, and was restored in 
      induced pluripotent stem cells. We identified hundreds of differentially 
      methylated regions proximal to genes involved in pluripotency and 
      differentiation, and widespread reduced methylation levels in fibroblasts 
      associated with lower transcriptional activity. These reference epigenomes 
      provide a foundation for future studies exploring this key epigenetic 
      modification in human disease and development.
FAU - Lister, Ryan
AU  - Lister R
AD  - Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, 
      California 92037, USA.
FAU - Pelizzola, Mattia
AU  - Pelizzola M
FAU - Dowen, Robert H
AU  - Dowen RH
FAU - Hawkins, R David
AU  - Hawkins RD
FAU - Hon, Gary
AU  - Hon G
FAU - Tonti-Filippini, Julian
AU  - Tonti-Filippini J
FAU - Nery, Joseph R
AU  - Nery JR
FAU - Lee, Leonard
AU  - Lee L
FAU - Ye, Zhen
AU  - Ye Z
FAU - Ngo, Que-Minh
AU  - Ngo QM
FAU - Edsall, Lee
AU  - Edsall L
FAU - Antosiewicz-Bourget, Jessica
AU  - Antosiewicz-Bourget J
FAU - Stewart, Ron
AU  - Stewart R
FAU - Ruotti, Victor
AU  - Ruotti V
FAU - Millar, A Harvey
AU  - Millar AH
FAU - Thomson, James A
AU  - Thomson JA
FAU - Ren, Bing
AU  - Ren B
FAU - Ecker, Joseph R
AU  - Ecker JR
LA  - eng
SI  - GEO/GSE16256
SI  - GEO/GSE17917
SI  - GEO/GSE18292
GR  - U01 1U01ES017166-01/ES/NIEHS NIH HHS/United States
GR  - R01 HG003523-01/HG/NHGRI NIH HHS/United States
GR  - R01 HG003523-02/HG/NHGRI NIH HHS/United States
GR  - R01 HG003523/HG/NHGRI NIH HHS/United States
GR  - U01 ES017166/ES/NIEHS NIH HHS/United States
GR  - R01 HG003523-03/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091014
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (DNA-Binding Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
CIN - Nature. 2009 Nov 19;462(7271):296-7. PMID: 19924205
MH  - Cell Line
MH  - Cluster Analysis
MH  - DNA/metabolism
MH  - *DNA Methylation
MH  - DNA-Binding Proteins/metabolism
MH  - Embryonic Stem Cells/metabolism
MH  - *Epigenesis, Genetic
MH  - Genome/*genetics
MH  - Humans
PMC - PMC2857523
MID - NIHMS192495
EDAT- 2009/10/16 06:00
MHDA- 2009/12/16 06:00
PMCR- 2010/05/19
CRDT- 2009/10/16 06:00
PHST- 2009/06/19 00:00 [received]
PHST- 2009/09/21 00:00 [accepted]
PHST- 2009/10/16 06:00 [entrez]
PHST- 2009/10/16 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/05/19 00:00 [pmc-release]
AID - nature08514 [pii]
AID - 10.1038/nature08514 [doi]
PST - ppublish
SO  - Nature. 2009 Nov 19;462(7271):315-22. doi: 10.1038/nature08514. Epub 2009 Oct 14.