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Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3341-3348
Identification and characterization of a new human ETS-family
transcription factor, TEL2, that is expressed in hematopoietic
tissues and can associate with TEL1/ETV6
Mark D. Potter,
Arjan Buijs,
Brent Kreider,
Luc van Rompaey, and
Gerard C. Grosveld
From the Department of Genetics, St Jude's Children Research
Hospital, Memphis, TN; and Human Genome Sciences, Inc, Rockville, MD.
The ETS family of proteins is a large group of transcription factors
implicated in many aspects of normal hematopoietic development, as well
as oncogenesis. For example, the TEL1/ETV6 (TEL1) gene is
required for normal yolk sac angiogenesis, adult bone marrow hematopoiesis, and is rearranged or deleted in numerous leukemias. This
report describes the cloning and characterization 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 kilobases (kb) in human chromosome
6p21. Unlike the ubiquitously expressed TEL1 gene, however,
TEL2 appears to be expressed predominantly in hematopoietic
tissues. Antibodies raised against the C-terminus of the TEL2 protein
were used to show that TEL2 localizes to the nucleus. All ETS
proteins can bind 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. Additionally, the TEL2
protein is capable of associating with itself and with TEL1 in
doubly transfected Hela cells, and this interaction is mediated through
the pointed (PNT) domain of TEL1. The striking similarities of
TEL2 to the oncogenic TEL1, its
expression in hematopoietic tissues, and its ability to associate with
TEL1 suggest that TEL2 may be an important hematopoietic
regulatory protein.
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