PMID- 19801979
OWN - NLM
STAT- MEDLINE
DCOM- 20091130
LR  - 20211020
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Linking)
VI  - 41
IP  - 11
DP  - 2009 Nov
TI  - DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid 
      restriction.
PG  - 1207-15
LID - 10.1038/ng.463 [doi]
AB  - DNA methylation is a dynamic epigenetic mark that undergoes extensive changes 
      during differentiation of self-renewing stem cells. However, whether these 
      changes are the cause or consequence of stem cell fate remains unknown. Here, we 
      show that alternative functional programs of hematopoietic stem cells (HSCs) are 
      governed by gradual differences in methylation levels. Constitutive methylation 
      is essential for HSC self-renewal but dispensable for homing, cell cycle control 
      and suppression of apoptosis. Notably, HSCs from mice with reduced DNA 
      methyltransferase 1 activity cannot suppress key myeloerythroid regulators and 
      thus can differentiate into myeloerythroid, but not lymphoid, progeny. A similar 
      methylation dosage effect controls stem cell function in leukemia. These data 
      identify DNA methylation as an essential epigenetic mechanism to protect stem 
      cells from premature activation of predominant differentiation programs and 
      suggest that methylation dynamics determine stem cell functions in tissue 
      homeostasis and cancer.
FAU - Broske, Ann-Marie
AU  - Broske AM
AD  - Max Delbruck Center for Molecular Medicine, Berlin, Germany.
FAU - Vockentanz, Lena
AU  - Vockentanz L
FAU - Kharazi, Shabnam
AU  - Kharazi S
FAU - Huska, Matthew R
AU  - Huska MR
FAU - Mancini, Elena
AU  - Mancini E
FAU - Scheller, Marina
AU  - Scheller M
FAU - Kuhl, Christiane
AU  - Kuhl C
FAU - Enns, Andreas
AU  - Enns A
FAU - Prinz, Marco
AU  - Prinz M
FAU - Jaenisch, Rudolf
AU  - Jaenisch R
FAU - Nerlov, Claus
AU  - Nerlov C
FAU - Leutz, Achim
AU  - Leutz A
FAU - Andrade-Navarro, Miguel A
AU  - Andrade-Navarro MA
FAU - Jacobsen, Sten Eirik W
AU  - Jacobsen SE
FAU - Rosenbauer, Frank
AU  - Rosenbauer F
LA  - eng
GR  - G0501838/MRC_/Medical Research Council/United Kingdom
GR  - G0701761/MRC_/Medical Research Council/United Kingdom
GR  - G0801073/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091004
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
SB  - IM
CIN - Nat Genet. 2009 Nov;41(11):1164-6. PMID: 19862008
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Cell Survival
MH  - DNA (Cytosine-5-)-Methyltransferase 1
MH  - DNA (Cytosine-5-)-Methyltransferases/genetics/metabolism
MH  - *DNA Methylation
MH  - *Epigenesis, Genetic
MH  - Erythroid Cells/*cytology/*metabolism
MH  - Gene Expression Regulation
MH  - Hematopoiesis
MH  - Hematopoietic Stem Cells/*cytology/metabolism
MH  - Homeostasis
MH  - Leukemia/metabolism
MH  - Mice
MH  - Multipotent Stem Cells/*cytology/metabolism
MH  - Neoplastic Stem Cells/metabolism
EDAT- 2009/10/06 06:00
MHDA- 2009/12/16 06:00
CRDT- 2009/10/06 06:00
PHST- 2009/04/03 00:00 [received]
PHST- 2009/08/25 00:00 [accepted]
PHST- 2009/10/06 06:00 [entrez]
PHST- 2009/10/06 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - ng.463 [pii]
AID - 10.1038/ng.463 [doi]
PST - ppublish
SO  - Nat Genet. 2009 Nov;41(11):1207-15. doi: 10.1038/ng.463. Epub 2009 Oct 4.