ARID1a Associates with Lymphoid-Restricted Transcription Factors and Has an Essential Role in T Cell Development
- 1 September 2020
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 205 (5), 1419-1432
- https://doi.org/10.4049/jimmunol.1900959
Abstract
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 β-selection. Our work highlights the critical importance of functional interactions between stage and lineage-restricted factors and the basic transcription machinery during lymphocyte differentiation.Funding Information
- Swedish Cancer Society (2017)
- Swedish Childhood Cancer Foundation (2017)
- Swedish Research Council (2018)
- Knut and Alice Wallenberg’s Foundation (2014-0089)
This publication has 88 references indexed in Scilit:
- The genetic landscape of mutations in Burkitt lymphomaNature Genetics, 2012
- Fast gapped-read alignment with Bowtie 2Nature Methods, 2012
- A critical role for TCF-1 in T-lineage specification and differentiationNature, 2011
- The human SWI/SNF complex associates with RUNX1 to control transcription of hematopoietic target genesJournal of Cellular Physiology, 2010
- Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell IdentitiesMolecular Cell, 2010
- Genome-wide Lineage-Specific Transcriptional Networks Underscore Ikaros-Dependent Lymphoid Priming in Hematopoietic Stem CellsImmunity, 2009
- ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250aProceedings of the National Academy of Sciences of the United States of America, 2008
- Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytesProceedings of the National Academy of Sciences of the United States of America, 2006
- Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growthNature, 2006
- Transcription factor GATA-3 is required for development of the T-cell lineageNature, 1996