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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1457-1464
IMMUNOBIOLOGY
Cloning of human early B-cell factor and identification of target
genes suggest a conserved role in B-cell development in man
and mouse
Ramiro Gisler,
Sten
Erik W. Jacobsen, and
Mikael Sigvardsson
From the Immunology Group, Cell and Molecular
Biology, Lund University; and the Stem Cell Laboratory, Lund
University Hospital, Lund, Sweden.
Early B-cell factor (EBF) is a helix-loop-helix transcription
factor suggested to be essential for B-cell development in the mouse.
Several genetic targets for EBF have been identified in mice, among
these the surrogate light chain 5 and the
signal-transducing molecules Ig (mb-1) and Ig
(B29). This article reports cloning of the human homologue
of EBF, hEBF. This protein has 93% sequence and 98.8%
amino acid homology with mouse EBF. The encoded protein binds DNA and
is expressed in cells of the B lineage, but not in cell populations
representing T lymphocytes or myeloid cells. It is also shown that
EBF-binding sites are functionally conserved in the human
mb-1 and B29 promoters because hEBF interacts
with these in the electrophoretic mobility shift assay (EMSA) and have the ability to increase the activity of reporter constructs under the
control of these promoters in nonlymphoid HeLa cells. A third genetic
target for hEBF is the promoter of the human surrogate light chain
14.1. This promoter contains 5 independent binding sites
capable of interacting with hEBF in the EMSA, and the activity of the
promoter was induced 24-fold in co-transfection experiments. These
findings suggest that the human homologue of mouse EBF displays conserved biochemical features as well as genetic targets, indicating that this protein also has an important role in human B-cell development.

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