Dynamic control of the T-cell specification gene regulatory network

Abstract

Specification of multipotent blood precursor cells in postnatal mice to become committed T-cell precursors involves a gene regulatory network of several interacting but functionally distinct modules. Many links of this network have been defined by perturbation tests and by functional genomics. However, using the network model to predict real-life kinetics of the commitment process is still difficult, partly due to the tenacity of repressive chromatin states, and to the ability of transcription factors to affect each other’s binding site choices through competitive recruitment to alternative sites (“coregulator theft”). To predict kinetics, future models will need to incorporate mechanistic information about chromatin state change dynamics and more sophisticated understanding of the proteomics and cooperative DNA site choices of transcription factor complexes.