Volume 272, Number 20,
Issue of May 16, 1997
pp. 12928-12937
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Human TEF-5 Is Preferentially Expressed in Placenta and Binds to
Multiple Functional Elements of the Human Chorionic Somatomammotropin-B
Gene Enhancer
(Received for publication, October 22, 1996, and in revised form, January 30, 1997)
Patrick
Jacquemin
§
,
Joseph A.
Martial
§
and
Irwin
Davidson
From the
Institut de Génétique et de
Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP,
Collège de France, B.P. 163-67404 Illkirch Cédex,
France and the § Laboratoire de Biologie Moléculaire
et de Génie Génétique, Institut de Chimie-B6,
Université de Liège, B-4000 Sart-Tilman, Belgium
We report the cloning of a cDNA encoding the
human transcription factor hTEF-5, containing the TEA/ATTS DNA binding
domain and related to the TEF family of transcription factors. hTEF-5 is expressed in skeletal and cardiac muscle, but the strongest expression is observed in the placenta and in placenta-derived JEG-3
choriocarcinoma cells. In correlation with its placental expression, we
show that hTEF-5 binds to several functional enhansons of the human
chorionic somatomammotropin (hCS)-B gene enhancer. We define a novel
functional element in this enhancer comprising tandemly repeated sites
to which hTEF-5 binds cooperatively. In the corresponding region of the
hCS-A enhancer, which is known to be inactive, this element is
inactivated by a naturally occurring single base mutation that disrupts
hTEF-5 binding. We further show that the binding of the previously
described placental protein f/chorionic somatomammotropin enhancer
factor-1 to TEF-binding sites is disrupted by monoclonal antibodies
directed against the TEA domain and that this factor is a proteolytic
degradation product of the TEF factors. These results strongly suggest
that hTEF-5 regulates the activity of the hCS-B gene enhancer.