Identification and characterization of a new human ETS-family transcription factor, TEL2, that is expressed in hematopoietic tissues and can associate with TEL1/ETV6

The ETS family of proteins is a large group of transcription factors implic ated in many aspects of normal hematopoietic development, as well as oncoge nesis. For example, the TEL 1/ETV6 (TEL1) gene is required for normal yolk sec angiogenesis, adult bone marrow hematopoiesis, and is rearranged or del eted in numerous leukemias. This report describes the cloning and character ization of a novel ETS gene that is highly related to TEL1 and is therefore called TEL2 The TEL2 gene consists of 8 exons spanning approximately 21 ki lobases (kb) in human chromosome 6p21, Unlike the ubiquitously expressed TE L1 gene, however, TEL2 appears to be expressed predominantly in hematopoiet ic tissues, Antibodies raised against the C-terminus of the TEL2 protein we re used to show that TEL2 localizes to the nucleus. All ETS proteins can bi nd DNA via the highly conserved ETS domain, which recognizes a purine-rich DNA sequence with a GGAA core motif, DNA binding assays show that TEL2 can bind the same consensus DNA binding sequence recognized by TEL1/ETV6, Addit ionally, the TEL2 protein is capable of associating with itself and with TE L1 in doubly transfected Hela cells, and this interaction is mediated throu gh the pointed (PNT) domain of TEL1, The striking similarities of TEL2 to t he oncogenic TEL1, its expression In hematopoietic tissues, and its ability to associate with TEL1 suggest that TEL2 may be an important hematopoietic regulatory protein. (Blood, 2000;95:3341-3348) (C) 2000 by The American So ciety of Hematology.