Identification and Characterization of BPTF, a Novel Bromodomain Transcription Factor

Abstract

The bromodomain is a 110-amino-acid conserved structural region associated with proteins that regulate signal-dependent, nonbasal transcription. The bromodomain can regulate histone acetyl transferase activity and interacts specifically with acetylated lysine residues. A key role for bromodomain proteins in maintaining normal proliferation is indicated by the implication of 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 predicted protein of 2781 amino acids, which, in addition to the bromodomain, harbors further motifs characteristic of a transcriptional coactivator: two PHD fingers and an extensive glutamine-rich acidic domain. There are several other regions that are conserved with the Caenorhabditis elegans putative protein F26H11, which may be functionally homologous. The novel gene, called BPTF, is expressed in all tissues examined as a 10.5-kb transcript. The protein has extensive identity with the smaller FAC1 protein, suggesting that the two either are derived from the same locus or are synonymous. BPTF has been mapped to 17q23. Functional domains found within BPTF are consistent with a role for this protein in hormonally regulated, chromatin-mediated regulation of transcription.