PMID- 21317239
OWN - NLM
STAT- MEDLINE
DCOM- 20110414
LR  - 20211020
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 25
IP  - 5
DP  - 2011 Mar 1
TI  - EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair 
      follicle homeostasis and wound repair.
PG  - 485-98
LID - 10.1101/gad.2019811 [doi]
AB  - Polycomb protein group (PcG)-dependent trimethylation on H3K27 (H3K27me3) 
      regulates identity of embryonic stem cells (ESCs). How H3K27me3 governs adult SCs 
      and tissue development is unclear. Here, we conditionally target H3K27 
      methyltransferases Ezh2 and Ezh1 to address their roles in mouse skin 
      homeostasis. Postnatal phenotypes appear only in doubly targeted skin, where 
      H3K27me3 is abolished, revealing functional redundancy in EZH1/2 proteins. 
      Surprisingly, while Ezh1/2-null hair follicles (HFs) arrest morphogenesis and 
      degenerate due to defective proliferation and increased apoptosis, epidermis 
      hyperproliferates and survives engraftment. mRNA microarray studies reveal that, 
      despite these striking phenotypic differences, similar genes are up-regulated in 
      HF and epidermal Ezh1/2-null progenitors. Featured prominently are (1) 
      PcG-controlled nonskin lineage genes, whose expression is still significantly 
      lower than in native tissues, and (2) the PcG-regulated Ink4a/Inkb/Arf locus. 
      Interestingly, when EZH1/2 are absent, even though Ink4a/Arf/Ink4b genes are 
      fully activated in HF cells, they are only partially so in epidermal progenitors. 
      Importantly, transduction of Ink4b/Ink4a/Arf shRNAs restores 
      proliferation/survival of Ezh1/2-null HF progenitors in vitro, pointing toward 
      the relevance of this locus to the observed HF phenotypes. Our findings reveal 
      new insights into Polycomb-dependent tissue control, and provide a new twist to 
      how different progenitors within one tissue respond to loss of H3K27me3.
FAU - Ezhkova, Elena
AU  - Ezhkova E
AD  - Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and 
      Development, The Rockefeller University, New York, New York 10065, USA;
FAU - Lien, Wen-Hui
AU  - Lien WH
FAU - Stokes, Nicole
AU  - Stokes N
FAU - Pasolli, H Amalia
AU  - Pasolli HA
FAU - Silva, Jose M
AU  - Silva JM
FAU - Fuchs, Elaine
AU  - Fuchs E
LA  - eng
GR  - 1K99AR057817-01/AR/NIAMS NIH HHS/United States
GR  - R01-AR31737/AR/NIAMS NIH HHS/United States
GR  - R01 AR050452/AR/NIAMS NIH HHS/United States
GR  - R01-AR050452/AR/NIAMS NIH HHS/United States
GR  - R01 AR031737/AR/NIAMS NIH HHS/United States
GR  - K99 AR057817/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110211
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p15)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
RN  - EC 1.5.- (Kdm6b protein, mouse)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
RN  - EC 2.1.1.43 (Ezh1 protein, mouse)
RN  - EC 2.1.1.43 (Ezh2 protein, mouse)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.1.1.43 (Polycomb Repressive Complex 2)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factor 1)
SB  - IM
MH  - ADP-Ribosylation Factor 1/genetics
MH  - Apoptosis/genetics
MH  - Cell Proliferation
MH  - Cell Survival/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p15/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Enhancer of Zeste Homolog 2 Protein
MH  - Epidermal Cells
MH  - Epidermis/transplantation
MH  - Gene Expression Regulation
MH  - Gene Knockout Techniques
MH  - Hair Follicle/cytology/*metabolism
MH  - Histone-Lysine N-Methyltransferase/genetics/*metabolism
MH  - Homeostasis/*genetics
MH  - Jumonji Domain-Containing Histone Demethylases/*metabolism
MH  - Methylation
MH  - Polycomb Repressive Complex 2
MH  - Skin Transplantation
MH  - Stem Cells/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Wound Healing/*genetics
PMC - PMC3049289
EDAT- 2011/02/15 06:00
MHDA- 2011/04/16 06:00
PMCR- 2011/09/01
CRDT- 2011/02/15 06:00
PHST- 2011/02/15 06:00 [entrez]
PHST- 2011/02/15 06:00 [pubmed]
PHST- 2011/04/16 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - gad.2019811 [pii]
AID - 10.1101/gad.2019811 [doi]
PST - ppublish
SO  - Genes Dev. 2011 Mar 1;25(5):485-98. doi: 10.1101/gad.2019811. Epub 2011 Feb 11.