Transcription factors regulate early T cell development via redeployment of other factors

Abstract

Establishment of cell lineage identity from multipotent progenitors is controlled by cooperative actions of lineage-specific and stably expressed transcription factors, combined with input from environmental signals. Lineage-specific master transcription factors activate and repress gene expression by recruiting consistently expressed transcription factors and chromatin modifiers to their target loci. Recent technical advances in genome-wide and multi-omics analysis have shed light on unexpected mechanisms that underlie more complicated actions of transcription factors in cell fate decisions. In this review, we discuss functional dynamics of stably expressed and continuously required factors, Notch and Runx family members, throughout developmental stages of early T cell development in the thymus. Pre-and post-commitment stagespecific transcription factors induce dynamic redeployment of Notch and Runx binding genomic regions. Thus, together with stage-specific transcription factors, shared transcription factors across distinct developmental stages regulate acquisition of T lineage identity.

The Route of Early T Cell Development: Crosstalk between Epigenetic and Transcription Factors

“…A pioneering role of Pu.1 has recently also been described in uncommitted T cells, wherein Pu.1 is able to bind to its closed target sites and initiate the opening of chromatin [ 176 , 180 ]. Pu.1 can recruit two other transcription factors, Satb1 and Runx1, to genomic sites, and it can activate or repress genes by displacement of these transcription factors along the genome [ 101 , 181 ]. Downregulation of Pu.1 expression is associated with the activation of Bcl11b, which defines the transition to committed cells and coincides with the loss of potential to develop toward myeloid lineages [ 82 , 92 ].…”

“…Notably, Cd4 and Cd8 gene expression is coordinated by the combined functions of epigenetic regulators and transcription factors that ensure proper silencing in immature T cells [ 194 ]. The mechanism of recruitment and redistribution of epigenetic and transcription factors has been elucidated in a DN3-like cell line [ 83 , 181 ]. The master regulator of T cell commitment, Bcl11b, regulates the expression of its target genes by nucleation of chromatin remodeling complexes such as PRC1, NuRD, REST complexes, and Runx1 to specific genomic sites [ 83 , 87 ].…”