TY - JOUR
T1 - Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex
AU - Rachez, Christophe
AU - Lemon, Bryan D.
AU - Suldan, Zalman
AU - Bromleigh, Virginia
AU - Gamble, Matthew
AU - Näär, Anders M.
AU - Erdjument-Bromage, Hediye
AU - Tempst, Paul
AU - Freedman, Leonard P.
PY - 1999/4/29
Y1 - 1999/4/29
N2 - Nuclear receptors modulate the transcription of genes in direct response to small lipophilic ligands. Binding to ligands induces conformational changes in the nuclear receptors that enable the receptors to interact with several types of cofactor that are critical for transcription activation (transactivation). We previously described a distinct set of ligand-dependent proteins called DRIPs, which interact with the vitamin D receptor (VDR); together, these proteins constitute a new cofactor complex. DRIPs bind to several nuclear receptors and mediate ligand-dependent enhancement of transcription by VDR and the thyroid-hormone receptor in cell-free transcription assays. Here we report the identities of thirteen DRIPs that constitute this complex, and show that the complex has a central function in hormone-dependent transactivation by VDR on chromatin templates. The DRIPs are almost indistinguishable from components of another new cofactor complex called ARC, which is recruited by other types of transcription activators to mediate transactivation on chromatin-assembled templates. Several DRIP/ARC subunits are also components of other potentially related cofactors, such as CRSP, NAT, SMCC and the mouse Mediator, indicating that unique classes of activators may share common sets or subsets of cofactors. The role of nuclear-receptor ligands may in part, be to recruit such a cofactor complex to the receptor and, in doing so, to enhance transcription of target genes.
AB - Nuclear receptors modulate the transcription of genes in direct response to small lipophilic ligands. Binding to ligands induces conformational changes in the nuclear receptors that enable the receptors to interact with several types of cofactor that are critical for transcription activation (transactivation). We previously described a distinct set of ligand-dependent proteins called DRIPs, which interact with the vitamin D receptor (VDR); together, these proteins constitute a new cofactor complex. DRIPs bind to several nuclear receptors and mediate ligand-dependent enhancement of transcription by VDR and the thyroid-hormone receptor in cell-free transcription assays. Here we report the identities of thirteen DRIPs that constitute this complex, and show that the complex has a central function in hormone-dependent transactivation by VDR on chromatin templates. The DRIPs are almost indistinguishable from components of another new cofactor complex called ARC, which is recruited by other types of transcription activators to mediate transactivation on chromatin-assembled templates. Several DRIP/ARC subunits are also components of other potentially related cofactors, such as CRSP, NAT, SMCC and the mouse Mediator, indicating that unique classes of activators may share common sets or subsets of cofactors. The role of nuclear-receptor ligands may in part, be to recruit such a cofactor complex to the receptor and, in doing so, to enhance transcription of target genes.
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U2 - 10.1038/19783
DO - 10.1038/19783
M3 - Article
C2 - 10235266
AN - SCOPUS:0033614417
SN - 0028-0836
VL - 398
SP - 824
EP - 828
JO - Nature
JF - Nature
IS - 6730
ER -