Protein proximity analysis unravels a complex interplay between lymphoid transcription factors and ARID1a in T-cell development.

Maturation of lymphoid cells is controlled by the action of stage and lineage restricted transcription factors, which work with the general transcription and chromatin remodelling machinery to regulate gene expression. To better understand this functional interplay we used BioID to identify proximity interaction partners for GATA3, TCF7, SPI1, HLF, IKZF1, PAX5, ID1 and ID2. We found that ARID1a, a BAF complex component, interacts with a number of these transcription factors. Consistent with this observation, deletion of Arid1a in early lymphoid progenitors resulted in reduced production of IgM+ immature B-cells, a pronounced block in early T-cell development, a 10-fold reduction in thymic cellularity, a reduction in CD4+CD8+ cells, and a developmental arrest in the DN3 to DN4 transition. Our work highlights the critical importance of functional interactions between stage and lineage restricted factors and the basic transcription machinery during lymphocyte differentiation. Overall design: T-cells of the developmental stage DN3 were sorted from Thymus of Arid1a Wt and KO mice. Sorted cells were later processed for RNA- and ATAC-seq. Differentally expressed in Arid1a WT vs. KO. Cells were identified using the RNA-seq data and Arid1a WT/KO ATAC signal was counted on DN3 and DN4 T-cell progenitor peak positions (peaks positions generated from data retrived from GSE100738).