Genomics and transcription analysis of human TFIID.

TFIID, a multisubunit protein comprised of TBP (TATA box-binding protein) and TAFIIs (TBP-associated factors), has a central role in transcription initiation at class II promoters. TAFIIs role as mediators of regulatory transcription factors, such as pRb and p53, and their involvement in signal transduction pathways suggest that some may participate in the control of cell proliferation and differentiation: therefore, they could be considered potential protooncogenes or antioncogenes. With the aim of starting to analyse these potential roles, we have determined the genomic position of nine human TAFII genes (TAFII250, TAFII135, TAFII100, TAFII80, TAFII55, TAFII43, TAFII31, TAFII28, TAFII20/15) and of two previously unknown sequences related to TAFII250 and TAFII31, respectively. Except for those encoding TAFII250 and TAFII31, these genes are present in a single copy and, with the exclusion of those for TAFII43 and TAFII28 (both at 6p21), are localized in different segments of the genome. Indeed, six of them map to a chromosomal region commonly altered in specific neoplasias, which defines them as candidates for involvement in oncogenesis. Our experiments also demonstrate that TAFII transcripts are synthesized ubiquitously, mostly at low levels similar to those of TBP. Interestingly, the amount of the major mRNA species detected by TAFII20/15 cDNA is higher, which suggests that the polypeptide it encodes may also perform functions independently of TFIID. TAFII isoforms, indicated by additional bands on Northern blots, may play a role in modulation of TFIID function. These data will be useful for analysing variations of TAFII mRNA phenotype during cell proliferation, differentiation and development, both normal and pathological.