ARID1a Associates with Lymphoid-Restricted Transcription Factors and Has an Essential Role in T Cell DevelopmentShow others and affiliations
2020 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 205, no 5, p. 1419-1432Article in journal (Refereed) Published
Abstract [en]
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 lineagerestricted 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 Aridla 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 Aridla-deficient mice suggested that the developmental block resided in the DN3a to DN3b transition, indicating a deficiency in beta-selection. Our work highlights the critical importance of functional interactions between stage and lineage-restricted factors and the basic transcription machinery during lymphocyte differentiation.
Place, publisher, year, edition, pages
AMER ASSOC IMMUNOLOGISTS , 2020. Vol. 205, no 5, p. 1419-1432
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:liu:diva-169214DOI: 10.4049/jimmunol.1900959ISI: 000562763400023PubMedID: 32747500OAI: oai:DiVA.org:liu-169214DiVA, id: diva2:1466650
Note
Funding Agencies|Swedish Cancer SocietySwedish Cancer Society [2017-258]; Swedish Childhood Cancer Foundation [2019-0020]; Swedish Research CouncilSwedish Research Council [2018-02448]; Stem Therapy program at Lund University; Knut and Alice Wallenbergs FoundationKnut & Alice Wallenberg Foundation [2014-0089]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR); Canada Foundation for InnovationCanada Foundation for Innovation; Princess Margaret Cancer FoundationUniversity of Toronto
2020-09-122020-09-122021-05-05