title: Transcription coactivator CBP has direct DNA binding activity and stimulates transcription factor DNA binding through small domains.
abstract: CBP and p300 are transcriptional coactivators that physically interact with diverse sequence-specific DNA-binding factors through conserved domains. To further investigate the functional roles of these protein-interaction domains in CBP/p300 regulation, we have identified multiple domains of CBP that interact with FKLF2 and the CH2 domain as a new p53 interacting domain of CBP. Functional studies demonstrate that several domains of CBP are capable of stimulating FKLF2 and p53 DNA binding. In addition, we found that CBP through distinct domain is able to bind DNA directly with no specificity. We identified a 51-residue domain in CBP that is capable of interacting with both transcription factors and DNA. We named this domain PDBD for protein and DNA binding domain. These results unveiled two novel activities of CBP. First, these highly conserved domains of CBP not only function to recruit CBP to the target promoter through interaction with DNA-bound transcription factors, but they also actively regulate the DNA binding activity of their interacting factors. Second, by directly interacting with DNA, CBP may orchestrate the formation of stable and promoter-committed transcriptional complexes through interactions with both proteins and promoter DNA.
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Box 357720, 1705 NE Pacific Streets, 98195, Seattle, WA, USA. szsong@u.washington.edu
authors.forename: Chao Zhong
authors.initials: CZ
authors.lastname: Song
authors.forename: Kimberly
authors.initials: K
authors.lastname: Keller
authors.forename: Yangchao
authors.initials: Y
authors.lastname: Chen
authors.forename: Ken
authors.initials: K
authors.lastname: Murata
authors.forename: George
authors.initials: G
authors.lastname: Stamatoyannopoulos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D004247:DNA / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA