p300, which was originally cloned as a nuclear binding target of the adenovirus E1A oncoprotein, forms a family with cyclic-AMP response element binding protein (CREB)-binding protein (CBP). p300/CBP are considered to be transcriptional coactivators that connect the basal transcriptional machinery to various DNA-binding transcriptional factors. p300/CBP are implicated in both cell differentiati...

The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional p300 gene. Animals nullizygous for p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embry...

Chromatin acetylation and deacetylation catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) are closely related to eukaryotic gene transcription. Although the binding of serum response factor (SRF) to the CArG boxes in the promoter region is necessary for SM22 expression, it has never been examined whether the local chromatin modification is involved in SM22 gene reg...

CBP/p300 transcriptional coactivators mediate gene expression by integrating cellular signals through interactions with multiple transcription factors. To elucidate the molecular and structural basis for CBP-dependent gene expression, we determined structures of the CBP TAZ1 and TAZ2 domains in complex with the transactivation domains (TADs) of signal transducer and activator of transcription 2...

Gonadal steroid hormones act in the brain to elicit changes in gene expression that result in profound effects on behavior and physiology. A variety of in vitro studies indicate that nuclear receptor coactivators are required for efficient transcriptional activity of steroid receptors. Two nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and cAMP response element binding pr...

CBP is a transcriptional coactivator required by many transcription factors for transactivation. Rubinstein-Taybi syndrome, which is an autosomal dominant syndrome characterized by abnormal pattern formation, has been shown to be associated with mutations in the Cbp gene. Furthermore, Drosophila CBP is required in hedgehog signaling for the expression of decapentapleigic, the Drosophila homolog...

The E2A gene encodes DNA-binding transcription factors, called E12 and E47, involved in cell specification and maturation. E2A is also involved in a chromosomal translocation that leads to the expression of an oncogenic transcription factor called E2A-PBX1 in cases of acute leukemia. In the work described here, we elucidate the interaction between E2A-PBX1 and transcriptional co-activators. We ...

Mammalian p300 and CBP are related transcriptional cofactors that possess histone acetyltransferase activity. Inactivation of CBP/p300 is critical for adenovirus E1A to induce oncogenic transformation and to inhibit differentiation, suggesting that these proteins are likely to play a role in cell growth and differentiation. Here we show that a Caenorhabditis elegans gene closely related to CBP/...

Drosophila melanogaster possesses a single gene, Dm myb, that is closely related to the vertebrate family of Myb genes, which encode transcription factors involved in regulatory decisions affecting cell proliferation, differentiation and apoptosis. In proliferating cells, the Dm myb gene product, DMyb, promotes both S-phase and M-phase, and acts to preserve diploidy by suppressing endoreduplica...

BACKGROUND Fetal alcohol exposure affects 1 in 100 children making it the leading cause of mental retardation in the US. It has long been known that alcohol affects cerebellum development and function. However, the underlying molecular mechanism is unclear. METHODOLOGY/PRINCIPAL FINDINGS We demonstrate that CREB binding protein (CBP) is widely expressed in granule and Purkinje neurons of the ...