PMID- 22037603
OWN - NLM
STAT- MEDLINE
DCOM- 20120709
LR  - 20211020
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 12
IP  - 12
DP  - 2011 Oct 30
TI  - Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the 
      histone methyltransferase Ezh2.
PG  - 1212-20
LID - 10.1038/ni.2136 [doi]
AB  - During B lymphopoiesis, recombination of the locus encoding the immunoglobulin 
      kappa-chain complex (Igk) requires expression of the precursor to the B cell antigen 
      receptor (pre-BCR) and escape from signaling via the interleukin 7 receptor 
      (IL-7R). By activating the transcription factor STAT5, IL-7R signaling maintains 
      proliferation and represses Igk germline transcription by unknown mechanisms. We 
      demonstrate that a STAT5 tetramer bound the Igk intronic enhancer (E(kappai)), which 
      led to recruitment of the histone methyltransferase Ezh2. Ezh2 marked 
      trimethylation of histone H3 at Lys27 (H3K27me3) throughout the kappa-chain joining 
      region (J(kappa)) to the kappa-chain constant region (C(kappa)). In the absence of Ezh2, IL-7 
      failed to repress Igk germline transcription. H3K27me3 modifications were lost 
      after termination of IL-7R-STAT5 signaling, and the transcription factor E2A 
      bound E(kappai), which resulted in acquisition of H3K4me1 and acetylated histone H4 
      (H4Ac). Genome-wide analyses showed a STAT5 tetrameric binding motif associated 
      with transcriptional repression. Our data demonstrate how IL-7R signaling 
      represses Igk germline transcription and provide a general model for 
      STAT5-mediated epigenetic transcriptional repression.
FAU - Mandal, Malay
AU  - Mandal M
AD  - Department of Medicine, Section of Rheumatology and Gwen Knapp Center for Lupus 
      and Immunology Research, University of Chicago, Chicago, Illinois, USA.
FAU - Powers, Sarah E
AU  - Powers SE
FAU - Maienschein-Cline, Mark
AU  - Maienschein-Cline M
FAU - Bartom, Elizabeth T
AU  - Bartom ET
FAU - Hamel, Keith M
AU  - Hamel KM
FAU - Kee, Barbara L
AU  - Kee BL
FAU - Dinner, Aaron R
AU  - Dinner AR
FAU - Clark, Marcus R
AU  - Clark MR
LA  - eng
GR  - P50 GM081892/GM/NIGMS NIH HHS/United States
GR  - R01 GM088847-03/GM/NIGMS NIH HHS/United States
GR  - GM088847/GM/NIGMS NIH HHS/United States
GR  - R01 GM088847-01A2/GM/NIGMS NIH HHS/United States
GR  - R01 CA099978/CA/NCI NIH HHS/United States
GR  - R01 GM088847-02/GM/NIGMS NIH HHS/United States
GR  - CA099978/CA/NCI NIH HHS/United States
GR  - R01 GM088847/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111030
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Histones)
RN  - 0 (IgK)
RN  - 0 (Immunoglobulins)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Tcf3 protein, mouse)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
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)
SB  - IM
CIN - Nat Immunol. 2011 Dec;12(12):1139-40. PMID: 22089213
MH  - Animals
MH  - Base Sequence
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Binding Sites/genetics
MH  - Binding, Competitive
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Cluster Analysis
MH  - Enhancer of Zeste Homolog 2 Protein
MH  - *Epigenesis, Genetic
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Histone-Lysine N-Methyltransferase/*metabolism
MH  - Histones/metabolism
MH  - Immunoglobulins/*genetics
MH  - Methylation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Polycomb Repressive Complex 2
MH  - Protein Binding
MH  - Receptors, Interleukin-7/metabolism
MH  - STAT5 Transcription Factor/*metabolism
MH  - Signal Transduction
PMC - PMC3233979
MID - NIHMS323927
EDAT- 2011/11/01 06:00
MHDA- 2012/07/10 06:00
PMCR- 2012/06/01
CRDT- 2011/11/01 06:00
PHST- 2011/07/28 00:00 [received]
PHST- 2011/09/09 00:00 [accepted]
PHST- 2011/11/01 06:00 [entrez]
PHST- 2011/11/01 06:00 [pubmed]
PHST- 2012/07/10 06:00 [medline]
PHST- 2012/06/01 00:00 [pmc-release]
AID - ni.2136 [pii]
AID - 10.1038/ni.2136 [doi]
PST - epublish
SO  - Nat Immunol. 2011 Oct 30;12(12):1212-20. doi: 10.1038/ni.2136.