Showing papers on "Bromodomain published in 1994"

Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor.

Abstract: The growth-controlling functions of the adenovirus E1A oncoprotein depend on its ability ot interact with a set of cellular proteins Among these are the retinoblastoma protein, p107, p130, and p300 We have isolated a cDNA encoding full-length human p300 and mapped the chromosomal location of the gene to chromosome 22q13 p300 contains three cysteine- and histidine-rich regions of which the most carboxy-terminal region interacts specifically with E1A In its center, p300 contains a bromodomain, a hallmark of certain transcriptional coactivators We have examined the ability of p300 to overcome the repressive effect of E1A on the SV40 enhancer We show that p300 molecules lacking an intact E1A-binding site can bypass E1A repression and restore to a significant extent the activity of the SV40 enhancer, even in the presence of high levels of E1A protein These results imply that p300 may function as a transcriptional adaptor protein for certain complex transcriptional regulatory elements

Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors.

Abstract: A selection for yeast mutants resistant to GAL4-VP16-induced toxicity previously identified two genes, ADA2 and ADA3, which may function as adaptors for some transcriptional activation domains and thereby facilitate activation. Here we identify two new genes by the same selection, one of which is identical to GCN5. We show that gcn5 mutants share properties with ada mutants, including slow growth, temperature sensitivity and reduced activation by the VP16 and GCN4 activation domains. Double mutant studies suggest that ADA2 and GCN5 function together in a complex or pathway. Moreover, we demonstrate that GCN5 binds to ADA2 both by the two-hybrid assay in vivo and by co-immunoprecipitation in vitro. This suggests that ADA2 and GCN5 are part of a heteromeric complex that mediates transcriptional activation. Finally, we demonstrate the functional importance of the bromodomain of GCN5, a sequence found in other global transcription factors such as the SWI/SNF complex and the TATA binding protein-associated factors. This domain is not required for the interaction between GCN5 and ADA2 and thus may mediate a more general activity of transcription factors.

Histone acetylation: facts and questions.

Abstract: The DNA of eukaryotic cells is organized in a complex with proteins, either as interphase chromatin or mitotic chromosomes. Nucleosomes, the structural subunits of chromatin, have long been considered as static structures, incompatible with processes occurring in chromatin. During the past few years it has become evident that the histone part of the nucleosome has important regulatory functions. Some of these functions are mediated by the N-terminal core histone domains which contain sites for posttranslational modifications, among them lysine residues for reversible acetylation. Recent results indicate that acetylation and deacetylation of N-terminal lysines of nucleosomal core histones represent a means of molecular communication between chromatin and the cellular signal transduction network, resulting in heritable epigenetic information. Data on enzymes involved in acetylation and the pattern of acetylated lysine sites on chromosomes, as well as genetic data on yeast transcriptional repression, suggest that acetylation may lead to structural transitions as well as specific signalling within distinct chromatin domains.