The zinc finger transcription factor, Bcl11b, is expressed in T cells and group 2 innate lymphoid cells (ILC2s) among hematopoietic cells. In early T-lineage cells, Bcl11b directly binds and represses the gene encoding the E protein antagonist, Id2, preventing pro-T cells from adopting innate-like fates. In contrast, ILC2s co-express both Bcl11b and Id2. To address this contradiction, we have directly compared Bcl11b action mechanisms in pro-T cells and ILC2s. We found that Bcl11b binding to regions across the genome shows distinct cell type–specific motif preferences. Bcl11b occupies functionally different sites in lineage-specific patterns and controls totally different sets of target genes in these cell types. In addition, Bcl11b bears cell type–specific post-translational modifications and organizes different cell type–specific protein complexes. However, both cell types use the same distal enhancer region to control timing of Bcl11b activation. Therefore, although pro-T cells and ILC2s both need Bcl11b for optimal development and function, Bcl11b works substantially differently in these two cell types.
Cell type–specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells
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Hiroyuki Hosokawa, Maile Romero-Wolf, Qi Yang, Yasutaka Motomura, Ditsa Levanon, Yoram Groner, Kazuyo Moro, Tomoaki Tanaka, Ellen V. Rothenberg; Cell type–specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells. J Exp Med 6 January 2020; 217 (1): e20190972. doi: https://doi.org/10.1084/jem.20190972
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