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| POLARITY-SPECIFIC ACTIVITIES OF RETINOIC ACID RECEPTORS DETERMINED BY A CO-REPRESSOR |
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| Author(s): KUROKAWA R, SODERSTROM M, HORLEIN A, HALACHMI S, BROWN M, ROSENFELD MG, GLASS CK |
| Source: NATURE Volume: 377 Issue: 6548 Pages: 451-454 Published: OCT 5 1995 |
| Times Cited: 420 References: 21 |
| Abstract: RETINOIC acid receptors (RARs) and retinoid-X receptors (RXRs) activate or repress transcription by binding as heterodimers to DNA-response elements that generally consist of two direct repeat half-sites of consensus sequence AGGTCA (reviewed in ref. 1). On response elements consisting of direct repeats spaced by five base pairs (DR + 5 elements), RAR/RXR heterodimers activate transcription in response to RAR-specific ligands, such as all-trans-retinoic acid (RA)(2). In contrast, on elements consisting of direct repeats spaced by one base pair (DR + 1 elements), RAR/RXR heterodimers exhibit little or no response to activating ligands and repress RXR-dependent transcription(3). Here we show that ligand-dependent transactivation by RAR on DR + 5 elements requires the dissociation of a new nuclear receptor co-repressor, N-CoR, and recruitment of the putative co-activators p140 and p160 (refs 4, 5). Surprisingly, on DR + 1 elements, N-CoR remains associated with RAR/RXR heterodimers even in the presence of RAR ligands, resulting in constitutive repression. These observations indicate that DNA-response elements can allosterically regulate RAR-co-repressor interactions to determine positive or negative regulation of gene expression. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CALIF SAN DIEGO, DEPT MED, LA JOLLA, CA 92093 USA
2. UNIV CALIF SAN DIEGO, DIV ENDOCRINOL & METAB, LA JOLLA, CA 92093 USA
3. UNIV CALIF SAN DIEGO, DIV CELLULAR & MOLEC MED, LA JOLLA, CA 92093 USA
4. UNIV CALIF SAN DIEGO, HOWARD HUGHES MED INST, LA JOLLA, CA 92093 USA
5. DANA FARBER CANC INST, DIV NEOPLAST DIS MECHANISMS, BOSTON, MA 02115 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: RY190 |
| ISSN: 0028-0836 |
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