Coregulatory proteins in steroid hormone receptor action: the role of chromatin high mobility group proteins HMG-1 and -2.

To directly activate specific gene expression, the progesterone receptor must bind to specific hormone response elements in target promoters. We have previously reported that progesterone receptor requires a nuclear factor, high mobility group 1 or 2 (HMG-1/-2) for high-affinity interaction with DNA in vitro and for full transcriptional activity in vivo. We have also observed that HMG-1/-2 selectively influences the activity of the steroid hormone class of nuclear receptors but does not affect other classes of nuclear receptors. This report is a summary of our published and unpublished studies to determine the effects of HMG-1/-2 on a broad range of nuclear receptor supergene family members and to define the mechanism for the specific effect of HMG-1/-2 on the steroid class of receptors. Our studies and available structural data suggest a model where the DNA binding domains of nonsteroid nuclear receptors contain a minor groove DNA interface, termed the C-terminal extension, that contributes to high-affinity DNA binding. Steroid receptors lack such a minor groove interface and therefore require an additional protein, HMG-1/-2, that functionally substitutes for the C-terminal extension to facilitate high-affinity interactions with DNA.