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Publication : BCL11B is positioned upstream of PLZF and RORγt to control thymic development of mucosal-associated invariant T cells and MAIT17 program.

First Author  Drashansky TT Year  2021
Journal  iScience Volume  24
Issue  4 Pages  102307
PubMed ID  33870128 Mgi Jnum  J:308565
Mgi Id  MGI:6717886 Doi  10.1016/j.isci.2021.102307
Citation  Drashansky TT, et al. (2021) BCL11B is positioned upstream of PLZF and RORgammat to control thymic development of mucosal-associated invariant T cells and MAIT17 program. iScience 24(4):102307
abstractText  Mucosal-associated invariant T (MAIT) cells recognize microbial riboflavin metabolites presented by MR1 and play role in immune responses to microbial infections and tumors. We report here that absence of the transcription factor (TF) Bcl11b in mice alters predominantly MAIT17 cells in the thymus and further in the lung, both at steady state and following Salmonella infection. Transcriptomics and ChIP-seq analyses show direct control of TCR signaling program and position BCL11B upstream of essential TFs of MAIT17 program, including RORgammat, ZBTB16 (PLZF), and MAF. BCL11B binding at key MAIT17 and at TCR signaling program genes in human MAIT cells occurred mostly in regions enriched for H3K27Ac. Unexpectedly, in human MAIT cells, BCL11B also bound at MAIT1 program genes, at putative active enhancers, although this program was not affected in mouse MAIT cells in the absence of Bcl11b. These studies endorse BCL11B as an essential TF for MAIT cells both in mice and humans.
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