Genomics and transcription analysis of human TFIID

Abstract

TFIID, a multisubunit protein comprised of TBP (TATA box-binding protein) and TAF_IIs (TBP-associated factors), has a central role in transcription initiation at class II promoters. TAF_IIs 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 TAF_II genes (TAF_II250, TAF_II135, TAF_II100, TAF_II80, TAF_II55, TAF_II43, TAF_II31, TAF_II28, TAF_II20/15) and of two previously unknown sequences related to TAF_II250 and TAF_II31, respectively. Except for those encoding TAF_II250 and TAF_II31, these genes are present in a single copy and, with the exclusion of those for TAF_II43 and TAF_II28 (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 TAF_II transcripts are synthesized ubiquitously, mostly at low levels similar to those of TBP. Interestingly, the amount of the major mRNA species detected by TAF_II20/15 cDNA is higher, which suggests that the polypeptide it encodes may also perform functions independently of TFIID. TAF_II 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 TAF_II mRNA phenotype during cell proliferation, differentiation and development, both normal and pathological.