title: Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex.
abstract: 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.
authors.affiliation: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Graduate School of Medical Sciences, Cornell University, New York, New York 10021, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rachez
authors.forename: B D
authors.initials: BD
authors.lastname: Lemon
authors.forename: Z
authors.initials: Z
authors.lastname: Suldan
authors.forename: V
authors.initials: V
authors.lastname: Bromleigh
authors.forename: M
authors.initials: M
authors.lastname: Gamble
authors.forename: A M
authors.initials: AM
authors.lastname: Näär
authors.forename: H
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: P
authors.initials: P
authors.lastname: Tempst
authors.forename: L P
authors.initials: LP
authors.lastname: Freedman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D002843:Chromatin / Q000502:physiology; D003001:Cloning, Molecular; D004330:Drosophila; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D018167:Receptors, Calcitriol / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors; D015533:Transcriptional Activation
chemical_list: C117286:CRSP protein, human; D002352:Carrier Proteins; D002843:Chromatin; C113182:DRIP, VDR interacting protein complex; D008024:Ligands; C538855:MED1 protein, human; C492160:MED14 protein, human; C492159:MED23 protein, human; C491863:MED4 protein, human; D046911:Macromolecular Substances; C538856:Med1 protein, mouse; C538713:Med17 protein, human; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; D009687:Nuclear Proteins; D018167:Receptors, Calcitriol; D015534:Trans-Activators; D014157:Transcription Factors