Transcription Factor Interactions in Genomic Nuclear Receptor Function

Abstract

Transcription factors (TF) regulate gene expression acting as DNA sequence-specific binding factors, orchestrating cofactor recruitment and assembly of the transcriptional machinery. Nuclear receptors, a ligand-inducible TF class, regulate a large proportion of the genome, yet achieve highly cell-specific and context-dependent transcription, despite their widespread expression. High-throughput genome-wide profiling of TF binding reveals a startling proportion of colocalized cell- and context-specific TF-binding patterns, implying TF interactions play a critical role in transcription. These interactions depend on the chromatin architecture, that predominantly acts to predetermine accessibility of TF-binding sites at regulatory elements. Here, we summarize recent findings that highlight the importance of combinatorial TF interactions in determining diverse nuclear receptor-mediated transcriptional responses, emphasizing the significance of chromatin structure in directing TF and nuclear receptor recruitment. Interactions between TFs are likely to be a general mechanism of regulatory factors, contributing to transcriptional control in health and disease.

KEYWORDS::

• androgen receptor
• cell specificity
• chromatin
• chromatin accessibility
• estrogen receptor
• genome wide
• glucocorticoid receptor
• nuclear receptor
• transcription factor

Financial & competing interests disclosure

This work was supported, in part, by the Needham Cooper Postgraduate Medicine Scholarship, University of Bristol, UK to Charlotte L George. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported, in part, by the Needham Cooper Postgraduate Medicine Scholarship, University of Bristol, UK to Charlotte L George. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.