Biomedical subjects

O V Devary

Publications and source records attributed to O V Devary.

4 recordsLinked to original sources

PubMed1991

RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements.

The retinoic acid receptor (RAR) requires coregulators to bind effectively to response elements in target genes. A strategy of sequential screening of expression libraries with a retinoic acid response element and RAR identified a cDNA encoding a coregulator highly related to RXR alpha. This protein, termed RXR beta, forms heterodimers with RAR, preferentially increasing its DNA binding and transcriptional activity on promoters containing retinoic acid, but not thyroid hormone or vitamin D, response elements. Remarkably, RXR beta also heterodimerizes with the thyroid hormone and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. RXR alpha also forms heterodimers with these receptors. These observations suggest that retinoid X receptors meet the criteria for biochemically characterized cellular coregulators and serve to selectively target the high affinity binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate DNA response elements.

Amino Acid Sequence↗

PubMed1990

Multiple cell type-specific proteins differentially regulate target sequence recognition by the alpha retinoic acid receptor.

Retinoic acid receptors appear to exert profound effects on vertebrate development by regulating the transcription of distinct sets of target genes within different cell types. Several lines of evidence are presented for the existence of multiple, cell type-specific nuclear proteins that function to differentially increase the binding affinity of the alpha retinoic acid receptor for a variety of response elements. These proteins, which we refer to as retinoic acid receptor coregulators, interact with the retinoic acid receptor via a common dimerization interface that overlaps with its ligand binding domain. These observations raise the intriguing possibility that coregulator proteins serve to restrict and/or direct the effects of retinoic acid receptors on patterns of gene expression during development.

Animals↗

PubMed1989

Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer.

We present evidence that the human thyroid hormone receptor forms a heterodimer with the human retinoic acid receptor. This interaction results in a cooperative increase in binding of the alpha retinoic acid receptor to a subset of thyroid hormone response elements. Mutations within the DNA binding domain or near the C-terminus abolish either receptor's ability to interact cooperatively on these elements. The thyroid hormone-retinoic acid receptor heterodimer exhibits novel transcriptional properties in that coexpression of both receptors at low levels in Green monkey kidney (CV1) cells results in a positive transcriptional effect on promoters containing a palindromic thyroid hormone response element, but has a surprisingly negative effect on a thyroid hormone response element derived from the alpha myosin heavy chain gene. These results suggest that by forming heterodimers, more elab-orate control of transcription can be achieved by creating receptor combinations with differing activities.

Amino Acid Sequence↗

PubMed1988

The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements.

We report that the thyroid hormone (T3) receptor binds to DNA recognition sequences that are variations of the palindromic motif 5'-TCAGGTCA.TGACCTGA-3', resulting in transcriptional activation in vivo. This sequence is identical to the vitellogenin A2 estrogen response element except for the absence of 3 bp at the center of dyad symmetry, which we have termed a "gap." The T3 receptor binds to estrogen response elements with high affinity in vitro, as well as to variations of the same sequence containing gaps of 1-6 bp. The T3 receptor not only fails to activate transcription from estrogen response elements in vivo, but inhibits estrogen-dependent transactivation. We propose that the T3 receptor binds to estrogen response elements in a transcriptionally inactive form and competes for estrogen receptor binding, resulting in a net decrease in gene expression. These data reveal that only a subset of T3 receptor DNA-binding elements function as T3 response elements.

Animals↗