PMID- 9858510
OWN - NLM
STAT- MEDLINE
DCOM- 19990122
LR  - 20190508
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 188
IP  - 12
DP  - 1998 Dec 21
TI  - Interleukin 7 receptor control of T cell receptor gamma gene rearrangement: role 
      of receptor-associated chains and locus accessibility.
PG  - 2233-41
AB  - VDJ recombination of T cell receptor and immunoglobulin loci occurs in immature 
      lymphoid cells. Although the molecular mechanisms of DNA cleavage and ligation 
      have become more clear, it is not understood what controls which target loci 
      undergo rearrangement. In interleukin 7 receptor (IL-7R)alpha-/- murine 
      thymocytes, it has been shown that rearrangement of the T cell receptor 
      (TCR)-gamma locus is virtually abrogated, whereas other rearranging loci are less 
      severely affected. By examining different strains of mice with targeted 
      mutations, we now observe that the signaling pathway leading from IL-7Ralpha to 
      rearrangement of the TCR-gamma locus requires the gammac receptor chain and the 
      gammac-associated Janus kinase Jak3. Production of sterile transcripts from the 
      TCR-gamma locus, a process that generally precedes rearrangement of a locus, was 
      greatly repressed in IL-7Ralpha-/- thymocytes. The repressed transcription was 
      not due to a lack in transcription factors since the three transcription factors 
      known to regulate this locus were readily detected in IL-7Ralpha-/- thymocytes. 
      Instead, the TCR-gamma locus was shown to be methylated in IL-7Ralpha-/- 
      thymocytes. Treatment of IL-7Ralpha-/- precursor T cells with the specific 
      histone deacetylase inhibitor trichostatin A released the block of TCR-gamma gene 
      rearrangement. This data supports the model that IL-7R promotes TCR-gamma gene 
      rearrangement by regulating accessibility of the locus via demethylation and 
      histone acetylation of the locus.
FAU - Durum, S K
AU  - Durum SK
AD  - Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, 
      Maryland 21702, USA.
FAU - Candeias, S
AU  - Candeias S
FAU - Nakajima, H
AU  - Nakajima H
FAU - Leonard, W J
AU  - Leonard WJ
FAU - Baird, A M
AU  - Baird AM
FAU - Berg, L J
AU  - Berg LJ
FAU - Muegge, K
AU  - Muegge K
LA  - eng
GR  - N01-C0-56000/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Chromatin)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (Transcription Factors)
RN  - 3X2S926L3Z (trichostatin A)
RN  - 63231-63-0 (RNA)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Jak3 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 3)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells
MH  - Chromatin/metabolism
MH  - DNA/metabolism
MH  - DNA Methylation
MH  - Enhancer Elements, Genetic/genetics
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor/drug effects/*genetics
MH  - Genes, RAG-1/genetics/physiology
MH  - Hematopoietic Stem Cells/*immunology/metabolism
MH  - Histone Deacetylase Inhibitors
MH  - Histone Deacetylases/metabolism
MH  - Hydroxamic Acids/pharmacology
MH  - Janus Kinase 3
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - RNA/biosynthesis
MH  - Receptors, Antigen, T-Cell, gamma-delta/*genetics/metabolism
MH  - Receptors, Interleukin-7/genetics/*metabolism
MH  - T-Lymphocytes/*immunology/metabolism
MH  - Thymus Gland/drug effects/embryology
MH  - Transcription Factors/metabolism
PMC - PMC2212428
EDAT- 1998/12/22 00:00
MHDA- 1998/12/22 00:01
PMCR- 1999/06/21
CRDT- 1998/12/22 00:00
PHST- 1998/12/22 00:00 [pubmed]
PHST- 1998/12/22 00:01 [medline]
PHST- 1998/12/22 00:00 [entrez]
PHST- 1999/06/21 00:00 [pmc-release]
AID - 10.1084/jem.188.12.2233 [doi]
PST - ppublish
SO  - J Exp Med. 1998 Dec 21;188(12):2233-41. doi: 10.1084/jem.188.12.2233.