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

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 endogenous E protein antagonist, Id2, expression to prevent pro-T cell from adopting an innate-like fate. In contrast, ILC2s co-express both Bcl11b and Id2. Here, to address this contradiction, we have directly compared Bcl11b action mechanisms in pro-T cells and ILC2s. We found that Bcl11b binds to distinctive genomic regions across the genome with cell-type specific motif preferences. Bcl11b occupies functionally different sites in lineage specific way and controls totally different sets of target genes, while both of cell types use the same distal enhancer region to control timing of Bcl11b activation. In addition, Bcl11b seems to have cell-type specific post-translational modifications and to organize differential protein complexes. Therefore, despite pro-T cells and ILC2s share Bcl11b for their optimal development and function, Bcl11b is able to regulate substantially different target genes. Overall design: ChIP-seq and RNA-seq