1998 Fiscal Year Final Research Report Summary
Research on Gene Expression Network via Coactivator CBP
| Project/Area Number |
09470037
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | The Institute of Physical and Chemical Research (RIKEN) |
|---|
Principal Investigator |
ISHII Shunsuke RIKEN,Molecular Genetics Laboratory, Chief Scientist, 分子遺伝学研究室, 主任研究員 (00124785)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MAEKAWA Toshio RIKEN,Molecular Genetics Laboratory, Scientist, 分子遺伝学研究室, 先任研究員 (90201764)
AKIMARU Hiroshi RIKEN,Molecular Genetics Laboratory, Scientist, 分子遺伝学研究室, 研究員 (70241247)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Keywords | transcriptional mediators / coactivator / CBP / Drosophila mutant / mouse mutant |
|---|
| Research Abstract |
Mutations in the human CBP gene appear to be associated with the Rubinstein-Taybi syndrome (RTS), a haploinsufficiency disorder characterized by abnormal pattern formation. However, the mechanism by which decreased CBP levels affect pattern formation is unclear. The hedgehog (hh) signaling pathway is an important determinant of pattern formation. cubitus interruptus (ci), a component of hh signaling, encodes a transcription factor homologous to the Gli family of proteins, and is required for induction of the hh-dependent expression of patched (ptc), decapentaplegic (dpp) and wingless (wg). Interestingly, a haploinsufficiency for the ci-related transcription factor Gli3 causes phenotypic changes in mice (known as "extra-toes") and humans (Greig's cephalopolysyndactyly syndrome) that have similarities to RTS.Our molecular and genetic studies indicated that Drosophila CBP (dCBP) functions as a co-activator of Ci. Thus, the dCBP-Ci interaction may provide clues for understanding the contribution of CBP to pattern formation in mammals. In addition, we showed that dCBP mutants fail to express the twist (twi) gene and generate twisted embryo. This is explained by results showing that dCBP is necessary for dl-mediated activation of the twi gene promoter. Furthermore, We showed that various abnormalities occur at high frequency in the skeletal system of heterozygous Cbp-deficient mice resulting from a C57BL/6-CBA x BALB/c cross. In support of a conserved signaling pathway for pattern formation in insects and mammals, the expression of Bmp7 was found to be reduced in the heterozygous mutants.
|
