Heterodimerization and deoxyribonucleic acid-binding properties of a retinoid X receptor-related factor.
The extent thyroid hormone receptors (TRs) bind to AGGTCA-related motifs as monomers and/or homodimers, and as heterodimers with retinoid X receptors (RXRs) depends on the number, spacing, and orientation of these half-sites. Here we show that recombinant RXR alpha affects TR binding to DNA in diverse ways; it enhances recombinant TR beta 1 binding to four-nucleotide-spaced direct repeat and palindromes but not to inverted palindromes. We also used an endogenous factor termed RXR alpha-RF that cross-reacted with antibodies to RXR alpha and copurified and formed heterodimers on DNA with rat liver TRs (mostly TR beta 1 isoform), supporting the fact that endogenous TRs are commonly heterodimers. RXR alpha-RF formed, like recombinant RXR alpha, heterodimers on DNA with vitamin D and retinoic acid but not estrogen receptors. RXR alpha-RF differed from recombinant RXR alpha in that it provoked enhancement of TR beta 1 binding to DNA irrespective of half-site architecture, was resistant to heating to 50 C, and did not form heterodimers with recombinant TR alpha 2 on four-nucleotide-spaced direct repeat. The overall enhancement of TR-DNA recognition by endogenous RXR alpha-RF, not found in studies with recombinant RXR alpha, might exemplify properties acquired in vivo by endogenous RXRs; this could promote wider DNA recognition by TRs and expand the thyroid hormone transcriptional influence in the cell.
Metabolic Research Unit, University of California, San Francisco, California 94143-0540.
R C
RC
Ribeiro
J W
JW
Apriletti
P M
PM
Yen
W W
WW
Chin
J D
JD
Baxter
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis* / Q000378:metabolism / Q000502:physiology*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone / Q000032:analysis / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000032:analysis* / Q000378:metabolism / Q000502:physiology*
D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors; D004247:DNA