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Cell type-specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells.

Hiroyuki Hosokawa | Maile Romero-Wolf | Qi Yang | Yasutaka Motomura | Ditsa Levanon | Yoram Groner | Kazuyo Moro | Tomoaki Tanaka | Ellen V Rothenberg
The Journal of experimental medicine | 2020

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.

Pubmed ID: 31653691

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI083514
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI135200
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD076915

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