GENOMICS AND TRANSCRIPTION ANALYSIS OF HUMAN TFIID

TFIID, a multisubunit protein comprised of TBP (TATA box-binding prote in) and TAF(II)s (TBP-associated factors), has a central role in trans cription initiation at class II promoters. TAF(II)s role as mediators of regulatory transcription factors, such as pRb and p53, and their in volvement in signal transduction pathways suggest that some may partic ipate in the control of cell proliferation and differentiation: theref ore, they could be considered potential protooncogenes or antioncogene s. With the aim of starting to analyse these potential roles, we have determined the genomic position of nine human TAF(II) genes (TAF(II)25 0, TAF(II)135, TAF(II)100, TAF(II)80, TAF(II)55, TAF(II)43, TAF(II)31, TAF(II)28, TAF(II)20/15) and of two previously unknown sequences rela ted to TAF(II)250 and TAF(II)31, respectively. Except for those encodi ng TAF(II)250 and TAF(II)31, these genes are present in a single copy and, with the exclusion of those for TAF(II)43 and TAF(II)28 (both at 6p21), are localized in different segments of the genome. Indeed, six of them map to a chromosomal region commonly altered in specific neopl asias, which defines them as candidates for in oncogenesis. Our experi ments also that TAF(II) transcripts are synthesized ubiquitously, most ly at low levels similar to those of TBP. Interestingly, the amount of the major mRNA species detected by TAF(II)20/15 cDNA is higher, which suggests that the polypeptide it encodes may also perform functions i ndependently of TFIID. TAF(II) isoforms, indicated by additional bands on Northern blots, may play a role in modulation of TFIID function. T hese data will be useful for analysing variations of TAF(II) mRNA phen otype during cell proliferation, differentiation and development, both normal and pathological.