Coregulators: From Whence Came These “Master Genes”

IT IS NOW OVER a decade since the first nuclear receptor (NR) coactivator, steroid receptor coactivator 1 (SRC-1), was cloned and discovered to be a new type of transcription factor that does not bind DNA, but rather, binds directly or indirectly to NRs to mediate their transcriptional potency. The NR coactivators belong to a class of molecules now termed “coregulators.” Employing an operational definition, we define coactivators as molecules that enhance transcription, and corepressors as molecules that repress transcription. Current evidence indicates that this operational definition can be modified by gene, cell, and signaling context for any one coregulator. Our current understanding is that NRs and other DNA-binding transcription factors (TFs) search out the target genes to be regulated by binding to specific DNA sequences (or other TFs at such sequences) termed “TF-response elements” (1 ); the second job of NRs is to recruit the coregulators that perform all of the subsequent reactions needed to ind...