title: Construction of a 1.2-Mb contig surrounding, and molecular analysis of, the human CREB-binding protein (CBP/CREBBP) gene on chromosome 16p13.3.
abstract: In the interest of cloning and analyzing the genes responsible for two very different diseases, the Rubinstein-Taybi syndrome (RTS) and acute myeloid leukemia (AML) associated with the somatic translocation t(8;16)(p11;p13.3), we constructed a high-resolution restriction map of contiguous cosmids (contig) covering 1.2 Mb of chromosome 16p13.3. By fluorescence in situ hybridization and Southern blot analysis, we assigned all tested RTS and t(8;16) translocation breakpoints to a 100-kb region. We have previously reported exact physical locations of these 16p breakpoints, which all disrupt one gene we mapped to this interval: the CREB-binding protein (CBP or CREBBP) gene. Intriguingly, mutations in the CBP gene are responsible for RTS as well as the t(8;16)-associated AML. CBP functions as an integrator in the assembly of various multiprotein regulatory complexes and is thus necessary for transcription in a broad range of transduction pathways. We report here the cloning, physical mapping, characterization, and full cDNA nucleotide sequence of the human CBP gene.
authors.affiliation: Department of Human Genetics, Leiden University, The Netherlands.
authors.forename: R H
authors.initials: RH
authors.lastname: Giles
authors.forename: F
authors.initials: F
authors.lastname: Petrij
authors.forename: H G
authors.initials: HG
authors.lastname: Dauwerse
authors.forename: A I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: T
authors.initials: T
authors.lastname: Lushnikova
authors.forename: G J
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: R H
authors.initials: RH
authors.lastname: Goodman
authors.forename: L L
authors.initials: LL
authors.lastname: Deaven
authors.forename: N A
authors.initials: NA
authors.lastname: Doggett
authors.forename: D J
authors.initials: DJ
authors.lastname: Peters
authors.forename: M H
authors.initials: MH
authors.lastname: Breuning
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D050882:CREB-Binding Protein; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D003360:Cosmids; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012415:Rubinstein-Taybi Syndrome / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human