Molecular basis for gene-specific transactivation by nuclear receptors

Nuclear receptors (NRs) are key transcriptional regulators of metazoan physiology and metabolism. Different NRs bind to similar or even identical core response elements; however, they regulate transcription in a highly receptor- and gene-specific manner. These differences in gene activation can most likely be accounted for by mechanisms involving receptor-specific interactions with DNA as well as receptor-specific interactions with protein complexes binding to adjacent and distant DNA sequences. Here, we review key molecular aspects of transactivation by NRs with special emphasis on the recent advances in the molecular mechanisms responsible for receptor- and gene-specific transcriptional activation. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.

Research Highlights
► The non-conserved regions of NRs contribute to gene specificity.
► DNA looping is a key aspect of NR signaling.
► NRs associate dynamically with target sites in the chromatin template.
► TF crosstalk is important for gene-specific transcriptional regulation by NRs.