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Isolation and Ex Vivo Culture of Vδ1+CD4+γδ T Cells, an Extrathymic αβT-cell Progenitor
Published on: December 7, 2015
Critical requirement of GABPalpha for normal T cell development
Shuyang Yu1, Dong-Mei Zhao, Raja Jothi
1Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
The Journal of Biological Chemistry
|February 9, 2010
Summary
GA binding protein (GABP) is crucial for T cell development. This study shows GABPalpha regulates T cell receptor (TCR) gene rearrangements, essential for normal thymocyte development.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- GA binding protein (GABP) is a transcription factor complex.
- GABPalpha binds DNA, GABPbeta has transactivation activity.
- GABP is implicated in T cell development and IL-7Ralpha regulation.
Purpose of the Study:
- To investigate the function of GABPalpha in early thymocyte development.
- To elucidate the role of GABP in T cell receptor (TCR) gene rearrangements.
Main Methods:
- Utilized GABPalpha conditional knock-out mice.
- Employed Lck-Cre transgene for GABPalpha ablation.
- Performed chromatin immunoprecipitation and RNA interference in thymocytes.
Main Results:
- GABPalpha deficiency blocked thymocyte development at the DN3 stage.
- GABPalpha associates with TCR rearrangement gene initiation sites.
- Knockdown of GABPalpha reduced expression of key DNA repair proteins (DNA ligase IV, Artemis, Ku80).
- Forced TCR expression, but not IL-7Ralpha, rescued the DN3 developmental block.
Conclusions:
- GABPalpha is essential for normal T cell development.
- GABP plays a critical role in TCR gene rearrangements.
- GABP regulates expression of genes vital for V(D)J recombination.
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