Identification and characterization of BPTF, a novel bromodomain transcription factor

The bromodomain is a 110-amino-acid conserved structural region associated with proteins that regulate signal-dependent, nonbasal transcription. The b romodomain can regulate histone acetyl transferase activity and interacts s pecifically with acetylated lysine residues. A key role for bromodomain pro teins in maintaining normal proliferation is indicated by the implication o f several bromodomain proteins in cancer, with four of these identified at translocation breakpoints. We searched EST databases for novel bromodomain genes. The sequence from one EST was used to initiate generation of a full- length clone from a testis cDNA library. The completed sequence encodes a p redicted protein of 2781 amino acids, which, in addition to the bromodomain , harbors further motifs characteristic of a transcriptional coactivator: t wo PHD fingers and an extensive glutamine-rich acidic domain. There are sev eral other regions that are conserved with the Caenorhabditis elegans putat ive protein F26H11, which may be functionally homologous. The novel gene, c alled BPTF, is expressed in all tissues examined as a 10.5-kb transcript. T he protein has extensive identity with the smaller FAC1 protein, suggesting that the two either are derived from the same locus or are synonymous. BPT F has been mapped to 17q23. Functional domains found within BPTF are consis tent with a role for this protein in hormonally regulated, chromatin-mediat ed regulation of transcription. (C) 2000 Academic Press.