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


ABSTRACT: 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.

SUBMITTER: Hosokawa H 

PROVIDER: S-EPMC7037248 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Hosokawa Hiroyuki H   Romero-Wolf Maile M   Yang Qi Q   Motomura Yasutaka Y   Levanon Ditsa D   Groner Yoram Y   Moro Kazuyo K   Tanaka Tomoaki T   Rothenberg Ellen V EV  

The Journal of experimental medicine 20200101 1


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 reg  ...[more]

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