PMID- 19349467
OWN - NLM
STAT- MEDLINE
DCOM- 20090514
LR  - 20220310
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 206
IP  - 4
DP  - 2009 Apr 13
TI  - CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7Ralpha gene 
      expression in early human thymopoiesis and leukemia.
PG  - 779-91
LID - 10.1084/jem.20081922 [doi]
AB  - Notch1 activation is essential for T-lineage specification of lymphomyeloid 
      progenitors seeding the thymus. Progression along the T cell lineage further 
      requires cooperative signaling provided by the interleukin 7 receptor (IL-7R), 
      but the molecular mechanisms responsible for the dynamic and lineage-specific 
      regulation of IL-7R during thymopoiesis are unknown. We show that active Notch1 
      binds to a conserved CSL-binding site in the human IL7R gene promoter and 
      critically regulates IL7R transcription and IL-7R alpha chain (IL-7Ralpha) 
      expression via the CSL-MAML complex. Defective Notch1 signaling selectively 
      impaired IL-7Ralpha expression in T-lineage cells, but not B-lineage cells, and 
      resulted in a compromised expansion of early human developing thymocytes, which 
      was rescued upon ectopic IL-7Ralpha expression. The pathological implications of 
      these findings are demonstrated by the regulation of IL-7Ralpha expression 
      downstream of Notch1 in T cell leukemias. Thus, Notch1 controls early T cell 
      development, in part by regulating the stage- and lineage-specific expression of 
      IL-7Ralpha.
FAU - Gonzalez-Garcia, Sara
AU  - Gonzalez-Garcia S
AD  - Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones 
      Cientificas, Universidad Autonoma de Madrid, Spain.
FAU - Garcia-Peydro, Marina
AU  - Garcia-Peydro M
FAU - Martin-Gayo, Enrique
AU  - Martin-Gayo E
FAU - Ballestar, Esteban
AU  - Ballestar E
FAU - Esteller, Manel
AU  - Esteller M
FAU - Bornstein, Rafael
AU  - Bornstein R
FAU - de la Pompa, Jose Luis
AU  - de la Pompa JL
FAU - Ferrando, Adolfo A
AU  - Ferrando AA
FAU - Toribio, Maria L
AU  - Toribio ML
LA  - eng
GR  - R01 CA120196/CA/NCI NIH HHS/United States
GR  - R01 CA120196-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090406
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Antigens, CD)
RN  - 0 (NOTCH1 protein, human)
RN  - 0 (Notch1 protein, mouse)
RN  - 0 (Receptor, Notch1)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (interleukin-7 receptor, alpha chain)
SB  - IM
EIN - J Exp Med. 2009 Jul 6;206(7):1633
MH  - Animals
MH  - Antigens, CD/immunology
MH  - Fetal Blood/immunology
MH  - Fetus/immunology
MH  - Flow Cytometry
MH  - *Gene Expression Regulation
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Infant, Newborn
MH  - Leukemia/genetics/*immunology
MH  - Mice
MH  - Organ Culture Techniques
MH  - Receptor, Notch1/immunology
MH  - Receptors, Interleukin-7/*genetics
MH  - T-Lymphocytes/*immunology
MH  - Thymus Gland/growth & development/*immunology
PMC - PMC2715119
EDAT- 2009/04/08 09:00
MHDA- 2009/05/15 09:00
PMCR- 2009/10/13
CRDT- 2009/04/08 09:00
PHST- 2009/04/08 09:00 [entrez]
PHST- 2009/04/08 09:00 [pubmed]
PHST- 2009/05/15 09:00 [medline]
PHST- 2009/10/13 00:00 [pmc-release]
AID - jem.20081922 [pii]
AID - 20081922 [pii]
AID - 10.1084/jem.20081922 [doi]
PST - ppublish
SO  - J Exp Med. 2009 Apr 13;206(4):779-91. doi: 10.1084/jem.20081922. Epub 2009 Apr 6.