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H‐2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes.
Author(s) -
Marks M.S.,
Hallenbeck P.L.,
Nagata T.,
Segars J.H.,
Appella E.,
Nikodem V.M.,
Ozato K.
Publication year - 1992
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1992.tb05187.x
Subject(s) - biology , retinoid x receptor , nuclear receptor , thyroid hormone receptor , retinoic acid , microbiology and biotechnology , dna binding domain , transcription factor , biochemistry , receptor , gene
H‐2RIIBP (RXR beta) is a member of the nuclear hormone receptor superfamily that activates transcription of MHC class I genes in response to retinoic acid (RA). Using chemical cross‐linking, co‐immunoprecipitation, gel mobility shift and streptavidin‐biotin DNA precipitation assays, we show that H‐2RIIBP formed heterodimers with thyroid hormone (T3) and RA receptors (T3R alpha and RAR alpha). H‐2RIIBP heterodimer formation required a conserved sub‐domain of its C‐terminal region, occurred independently of target DNA and was much more efficient than either T3R alpha/RAR alpha heterodimer or H‐2RIIBP homodimer formation. Heterodimers displayed enhanced binding to target DNA elements and contacted DNA in a manner distinct from that of homodimers. A functional role for heterodimers in vivo was demonstrated by synergistic enhancement of MHC class I transcription following co‐transfection of H‐2RIIBP with T3R alpha or RAR alpha. We provide biochemical evidence that H‐2RIIBP formed heterodimers with several naturally occurring nuclear proteins. The results suggest that H‐2RIIBP, by virtue of its ability to heterodimerize, enhances combinatorial diversity and versatility in gene regulation mediated by nuclear hormone receptors.