Enhancer function regulated by combinations of transcription factors and cofactors

Regulation of the expression of diverse genes is essential for making possible the complexity of higher organisms, and the temporal and spatial regulation of gene expression allows for the alteration of cell types and growth patterns. A critical component of this regulation is the DNA sequence‐specific binding of transcription factors (TFs). However, most TFs do not independently participate in gene transcriptional regulation, because they lack an effector function. Instead, TFs are thought to work by recruiting cofactors, including Mediator complex (Mediator), chromatin‐remodeling complexes (CRCs), and histone‐modifying complexes (HMCs). Mediator associates with the majority of transcribed genes and acts as an integrator of multiple signals. On the other hand, CRCs and HMCs are selectively recruited by TFs. Although all the pairings between TFs and CRCs or HMCs are not fully known, there are a growing number of established TF–CRC and TF–HMC combinations. In this review, we focused on the most important of these pairings and discuss how they control gene expression. Pioneer transcription factor 1 (TF1) binds closed chromatin and represses transcription by recruiting the HDAC complex until cell reprogramming is initiated. TF1 exchanges its binding partner for the chromatin‐remodeling complex (CRC), which remodels chromatin structure. Mediator integrates activation signals from both TFs, promotes preinitiation complex assembly, and also participates in the ensuing transcriptional elongation process.