GENOMIC STRUCTURE AND CHROMOSOMAL LOCALIZATION OF THE NOVEL ETS FACTOR, PE-2 (ERF)

The members of the ETS family of transcription factors are grouped bec ause they share a highly conserved DNA binding domain. These factors a re involved in growth factor pathways and regulate both proliferation and differentiation. To identify ETS factors that may be involved in e arly hematopoietic progenitor regulation, we isolated a novel member o f the ETS family by reverse transcriptase-PCR of the conserved DNA bin ding domain using degenerate oligonucleotides. This gene directs the s ynthesis of a 2704-nucleotide transcript whose largest open reading fr ame encodes a 548-amino-acid protein. Northern blot analysis reveals u biquitous expression in all human tissues and cell lines tested, with highest levels in the testis, ovary, pancreas, and heart. Comparison o f this gene with the available databases reveals very significant homo logy to the ETS factor PE-1 and probable near-identity with the recent ly cloned factor ERF. The PE-2 gene is composed of four exons spanning over 9 kb of genomic DNA. Sequence analysis of the promoter region re veals a GC-rich sequence without a TATA motif and with putative bindin g motifs for CREB, c-myb, and AP-1 factors. Using mouse-human somatic hybrids and FISH analysis, the PE-2 gene is localized to human chromos ome 19q13.2, a region involved in translocations and deletions in leuk emias and several solid tumors, suggesting that this novel ETS factor may play a role in carcinogenesis. (C) 1997 Academic Press.