Retinoic acid receptors β and γ do not repress, but instead activate target gene transcription in both the absence and presence of hormone ligand

Herborg Hauksdottir, Behnom Farboud, Martin L. Privalsky

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Retinoic acid receptors (RARs) are important mediators of retinoid signaling in morphogenesis, development, and cell differentiation. Three major isotypes of RARs, denoted α, β, and γ, have been identified, each encoded by a distinct genetic locus. Although RARα, RARβ, and RARγ share many structural and functional features, these three isotypes are known to play unique, as well as overlapping, roles in physiology and development. We report here that the three RAR isotypes display different transcriptional properties in the absence of hormone ligand; under these conditions, RARα is a strong repressor of target gene expression, whereas both RARβ and RARγ fail to repress and instead are able to mediate substantial levels of hormone-independent transcriptional activation. These differing transcriptional properties appear to reflect the differing abilities of the three RAR isotypes to interact with the SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor protein: RARα binds to SMRT strongly both in vitro and in vivo, whereas RARβ and RARγ interact only weakly with SMRT. The ability to repress or to activate transcription in the absence of hormone maps predominantly to isotype-specific differences in the sequence of helix 3 within the hormone binding domain of the RARs, and the transcriptional properties of one isotype can be exchanged with that of another by exchanging portions of helix 3. The different transcriptional properties of RARα, RARβ, and RARγ, in the absence of hormone contribute to the distinctive biological functions of these proteins and provide a rationale for the strong conservation of the three distinct isotypes during the vertebrate evolutionary radiation.

Original languageEnglish (US)
Pages (from-to)373-385
Number of pages13
JournalMolecular Endocrinology
Volume17
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

Retinoic Acid Receptors
Hormones
Ligands
Genes
Nuclear Receptor Co-Repressor 2
Co-Repressor Proteins
Genetic Loci
Retinoids

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Retinoic acid receptors β and γ do not repress, but instead activate target gene transcription in both the absence and presence of hormone ligand. / Hauksdottir, Herborg; Farboud, Behnom; Privalsky, Martin L.

In: Molecular Endocrinology, Vol. 17, No. 3, 01.03.2003, p. 373-385.

Research output: Contribution to journalArticle

@article{97c58c444f1a4aaa851abaff33152532,
title = "Retinoic acid receptors β and γ do not repress, but instead activate target gene transcription in both the absence and presence of hormone ligand",
abstract = "Retinoic acid receptors (RARs) are important mediators of retinoid signaling in morphogenesis, development, and cell differentiation. Three major isotypes of RARs, denoted α, β, and γ, have been identified, each encoded by a distinct genetic locus. Although RARα, RARβ, and RARγ share many structural and functional features, these three isotypes are known to play unique, as well as overlapping, roles in physiology and development. We report here that the three RAR isotypes display different transcriptional properties in the absence of hormone ligand; under these conditions, RARα is a strong repressor of target gene expression, whereas both RARβ and RARγ fail to repress and instead are able to mediate substantial levels of hormone-independent transcriptional activation. These differing transcriptional properties appear to reflect the differing abilities of the three RAR isotypes to interact with the SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor protein: RARα binds to SMRT strongly both in vitro and in vivo, whereas RARβ and RARγ interact only weakly with SMRT. The ability to repress or to activate transcription in the absence of hormone maps predominantly to isotype-specific differences in the sequence of helix 3 within the hormone binding domain of the RARs, and the transcriptional properties of one isotype can be exchanged with that of another by exchanging portions of helix 3. The different transcriptional properties of RARα, RARβ, and RARγ, in the absence of hormone contribute to the distinctive biological functions of these proteins and provide a rationale for the strong conservation of the three distinct isotypes during the vertebrate evolutionary radiation.",
author = "Herborg Hauksdottir and Behnom Farboud and Privalsky, {Martin L.}",
year = "2003",
month = "3",
day = "1",
doi = "10.1210/me.2002-0340",
language = "English (US)",
volume = "17",
pages = "373--385",
journal = "Molecular Endocrinology",
issn = "0888-8809",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Retinoic acid receptors β and γ do not repress, but instead activate target gene transcription in both the absence and presence of hormone ligand

AU - Hauksdottir, Herborg

AU - Farboud, Behnom

AU - Privalsky, Martin L.

PY - 2003/3/1

Y1 - 2003/3/1

N2 - Retinoic acid receptors (RARs) are important mediators of retinoid signaling in morphogenesis, development, and cell differentiation. Three major isotypes of RARs, denoted α, β, and γ, have been identified, each encoded by a distinct genetic locus. Although RARα, RARβ, and RARγ share many structural and functional features, these three isotypes are known to play unique, as well as overlapping, roles in physiology and development. We report here that the three RAR isotypes display different transcriptional properties in the absence of hormone ligand; under these conditions, RARα is a strong repressor of target gene expression, whereas both RARβ and RARγ fail to repress and instead are able to mediate substantial levels of hormone-independent transcriptional activation. These differing transcriptional properties appear to reflect the differing abilities of the three RAR isotypes to interact with the SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor protein: RARα binds to SMRT strongly both in vitro and in vivo, whereas RARβ and RARγ interact only weakly with SMRT. The ability to repress or to activate transcription in the absence of hormone maps predominantly to isotype-specific differences in the sequence of helix 3 within the hormone binding domain of the RARs, and the transcriptional properties of one isotype can be exchanged with that of another by exchanging portions of helix 3. The different transcriptional properties of RARα, RARβ, and RARγ, in the absence of hormone contribute to the distinctive biological functions of these proteins and provide a rationale for the strong conservation of the three distinct isotypes during the vertebrate evolutionary radiation.

AB - Retinoic acid receptors (RARs) are important mediators of retinoid signaling in morphogenesis, development, and cell differentiation. Three major isotypes of RARs, denoted α, β, and γ, have been identified, each encoded by a distinct genetic locus. Although RARα, RARβ, and RARγ share many structural and functional features, these three isotypes are known to play unique, as well as overlapping, roles in physiology and development. We report here that the three RAR isotypes display different transcriptional properties in the absence of hormone ligand; under these conditions, RARα is a strong repressor of target gene expression, whereas both RARβ and RARγ fail to repress and instead are able to mediate substantial levels of hormone-independent transcriptional activation. These differing transcriptional properties appear to reflect the differing abilities of the three RAR isotypes to interact with the SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor protein: RARα binds to SMRT strongly both in vitro and in vivo, whereas RARβ and RARγ interact only weakly with SMRT. The ability to repress or to activate transcription in the absence of hormone maps predominantly to isotype-specific differences in the sequence of helix 3 within the hormone binding domain of the RARs, and the transcriptional properties of one isotype can be exchanged with that of another by exchanging portions of helix 3. The different transcriptional properties of RARα, RARβ, and RARγ, in the absence of hormone contribute to the distinctive biological functions of these proteins and provide a rationale for the strong conservation of the three distinct isotypes during the vertebrate evolutionary radiation.

UR - http://www.scopus.com/inward/record.url?scp=0037341724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037341724&partnerID=8YFLogxK

U2 - 10.1210/me.2002-0340

DO - 10.1210/me.2002-0340

M3 - Article

C2 - 12554770

AN - SCOPUS:0037341724

VL - 17

SP - 373

EP - 385

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 3

ER -