title: Nuclear accessory factors enhance the binding of progesterone receptor to specific target DNA.
abstract: The human progesterone receptor (PR) is dependent upon hormone and a nuclear accessory factor(s) for maximal binding to progesterone response elements (PRES) in vitro. Recombinant full-length PR, expressed in a baculovirus system and purified to apparent homogeneity, was used as a substrate to isolate and identify the accessory factor(s). The major PRE binding enhancement activity present in nuclear extracts was shown to be associated with the high mobility group chromatin protein HMG-1. Moreover, HMG-1 was equally effective in enhancing the DNA binding of both the A and B isoforms of PR. Enhancement of PRE binding was highly selective for HMG-1 as a single purified protein and was not mimicked by a general protein stabilization effect. In gel mobility shift assays, it appeared that HMG-1 enhanced PRE binding without stably participating as a component of the final DNA-PR complex, suggesting that HMG-1 acts indirectly by modifying the PR protein or the target DNA. HMG-1 is a sequence-independent DNA binding protein that recognizes distorted DNA structures and is also able to promote further distortions by bending DNA. Enhancement of PRE binding was found to be intrinsic to the conserved DNA binding domain of HMG-1 suggesting that HMG-1 acts by promoting a structural alteration in the target PRE-DNA.
authors.affiliation: Department of Pathology, University of Colorado Cancer Center, Denver 80262-0216.
authors.forename: P
authors.initials: P
authors.lastname: Prendergast
authors.forename: S A
authors.initials: SA
authors.lastname: Oñate
authors.forename: K
authors.initials: K
authors.lastname: Christensen
authors.forename: D P
authors.initials: DP
authors.lastname: Edwards
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*
chemical_list: D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D011980:Receptors, Progesterone; D011374:Progesterone; D004247:DNA