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(Received for publication, April 26, 1996, and in revised form, June 27, 1996)
From the A novel member of the winged helix (formerly
HNF-3/Forkhead) transcriptional regulatory family, termed
Genesis, was isolated and characterized. Putative
translation of the complete cDNA revealed the winged helix DNA
binding domain to be centrally located within the protein, with regions
on either side that contain known transcriptional regulatory motifs.
Extensive Northern analysis of Genesis found that the
message was exclusively expressed in embryonic stem cells or their
malignant equivalent, embryonal carcinoma cells. The
Genesis transcript was down-regulated when these cells were
stimulated to differentiate. DNA sequences that Genesis
protein would interact with were characterized and were found to
contain a consensus similar to that found in an embryonic stem cell
enhancer sequence. Co-transfection experiments revealed that
Genesis is a transcriptional repressor. Genesis
mapped to mouse chromosome 4 in a region syntenic with human chromosome
1p31, a site of nonrandom abnormalities in germ cell neoplasia,
neuroblastoma, and acute lymphoblastic leukemia. Genesis is
a candidate for regulating the phenotype of normal or malignant
embryonic stem cells.
Volume 271, Number 38,
Issue of September 20, 1996
pp. 23126-23133
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
,
,
,
and
Division of Hematology/Oncology and the
Walther Oncology Center, IB 442, Indiana University Medical Center,
Indianapolis, Indiana 46202-5121, the § Department of
Biochemistry, University of Illinois College of Medicine, Chicago,
Illinois 60612-7334, 
Krannert Institute of Cardiology, Indiana
University Medical Center, Indianapolis, Indiana 46202, 
Mammalian Genetics Laboratory, ABL-Basic
Research Program, NCI, National Institutes of Health, Frederick
Cancer Research and Development Center, Frederick, Maryland 21702, and
the Department of Microbiology/Immunology, MS
252, Indiana University Medical Center,
Indianapolis, Indiana 46202-5120
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