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BCL11B AND COMBINATORIAL RESOLUTION OF CELL FATE IN THE T-CELL GENE REGULATORY NETWORK

ABSTRACT: T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining the roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing the basis for a comprehensively updated model of the T-cell specification gene regulatory network (GRN). However, the role of lineage commitment factor Bcl11b has been unclear. We use Self-Organizing Maps (SOM) on 63 RNA-seq datasets from normal and perturbed T-cell development to identify positive and negative regulation targets of Bcl11b during commitment and relate them to other regulomes. Both activation and repression targets can be bound by Bcl11b in vivo, but both depend strongly on developmental context. The newly clarified role of Bcl11b distinguishes discrete components of commitment, resolving how innate lymphoid cell, myeloid and dendritic, and B cell fate alternatives are excluded by different mechanisms.

ORGANISM(S): Mus musculus

PROVIDER: GSE93572 | GEO | 2017/02/13

SECONDARY ACCESSION(S): PRJNA361158

REPOSITORIES: GEO

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