Pre-programmed regulatory networks and poised chromatin potentiate lineage-specific differentiation of CD4+ T cells

Abstract

How the interactions of transcription factors (TFs) with specific regions of chromatin control the basis for cellular function and identity remains an open question. Here, analysis of regions of accessible chromatin, which are identified globally across T cell subtypes, demonstrates that the chromatin of naïve CD4 T cells is poised towards the acquisition of effector function. Additionally, the development of genome-wide maps of in vivo transcription factor footprints allows the assembly of extensive regulatory networks comprising connections among 476 sequence-specific transcription factors, demonstrating the dynamics of these connections across mature human CD4 T cell subtypes. Well-characterized subset-specific TFs show prominent occupancy in subset-specific networks. Moreover, conserved regulatory architectures act through these subset-specific regulatory factors, to potentiate, rather than direct, mature CD4 T cell differentiation.