ARID1a Associates with Lymphoid-Restricted Transcription Factors and Has an Essential Role in T Cell Development.
J Immunol
; 205(5): 1419-1432, 2020 09 01.
Article
en En
| MEDLINE
| ID: mdl-32747500
Maturation of lymphoid cells is controlled by the action of stage and lineage-restricted transcription factors working in concert with the general transcription and chromatin remodeling machinery to regulate gene expression. To better understand this functional interplay, we used Biotin Identification in human embryonic kidney cells to identify proximity interaction partners for GATA3, TCF7 (TCF1), SPI1, HLF, IKZF1, PAX5, ID1, and ID2. The proximity interaction partners shared among the lineage-restricted transcription factors included ARID1a, a BRG1-associated factor complex component. CUT&RUN analysis revealed that ARID1a shared binding with TCF7 and GATA3 at a substantial number of putative regulatory elements in mouse T cell progenitors. In support of an important function for ARID1a in lymphocyte development, deletion of Arid1a in early lymphoid progenitors in mice resulted in a pronounced developmental arrest in early T cell development with a reduction of CD4+CD8+ cells and a 20-fold reduction in thymic cellularity. Exploring gene expression patterns in DN3 cells from Wt and Arid1a-deficient mice suggested that the developmental block resided in the DN3a to DN3b transition, indicating a deficiency in ß-selection. Our work highlights the critical importance of functional interactions between stage and lineage-restricted factors and the basic transcription machinery during lymphocyte differentiation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Linfocitos
/
Linfocitos T CD4-Positivos
/
Linfocitos T CD8-positivos
/
Proteínas de Unión al ADN
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Estados Unidos