Dynamics of coactivator recruitment and chromatin modifications during nuclear receptor mediated transcription

Abstract

The mechanisms and interplay of coactivators that underlie transcription activation is a critical avenue of investigation in biology today. Using nuclear receptor (NR) mediated transcription activation as a model, the nature of coactivator recruitment and chromatin modifications has been found to be highly dynamic. Progress in understanding the kinetics and regulation of coactivator recruitment, and subsequent effects on transcriptional readout, has greatly improved our understanding of nuclear receptor mediated transcription, the subject of discussion in this 'At the Cutting Edge' review.

Figure 1. Dynamic association of cofactors with NR target promoters

Nuclear receptor (NR) mediated transcription activation is accompanied by dynamic association of chromatin remodeling complexes (CRC), co-activators, Mediator, general transcription factors (GTFs) and the RNA pol II (POL II) machinery with the promoter. These factors are recruited to chromatin via various protein-protein and protein-DNA interactions (blue double arrows ↔). The dynamic exchange of factors on target promoters plays an important role in modulating expression of target genes (grey double arrows↔). The combinatorial action of the NR, co-activators, CRC and the Mediator complex leads to changes in histone modifications (green nucleosomes) and chromatin remodeling/nucleosome loss, leading to robust transcriptional output (black arrow). In addition to these productive cycles of transcription, stochastic interaction of factors with various regions of the genome may occur, but not necessarily leading to productive transcription (grey double arrows↔).