Construction of a 1.2-Mb contig surrounding, and molecular analysis of, the human CREB-binding protein (CBP/CREBBP) gene on chromosome 16p13.3.
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.
Giles
R H
RH
Department of Human Genetics, Leiden University, The Netherlands.
Petrij
F
F
Dauwerse
H G
HG
den Hollander
A I
AI
Lushnikova
T
T
van Ommen
G J
GJ
Goodman
R H
RH
Deaven
L L
LL
Doggett
N A
NA
Peters
D J
DJ
Breuning
M H
MH
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
D017931:DNA Primers; D018076:DNA, Complementary; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human