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Volume 271,
Number 19,
Issue of May 10, 1996 pp. 11392-11399
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Induction of
c-Erb A-AP-1 Interactions and c-Erb A Transcriptional Activity in
Myoblasts by RXR
CONSEQUENCES FOR MUSCLE DIFFERENTIATION
(Received for publication, January 11, 1996; and in revised form, February 29,
1996)
Isabelle
Cassar-Malek ,
Sophie
Marchal,
Pierrick
Rochard ,
François
Casas ,
Chantal
Wrutniak,
Jacques
Samarut
,
Gérard
Cabello
We have previously shown that c-Erb A and v-Erb A display a
cell-specific activity in avian myoblasts. In this work, we have
compared the molecular basis of thyroid hormone action in HeLa cells
and in QM7 myoblasts. The transcriptional activity of c-Erb A 1
through a palindromic thyroid hormone response element (TRE) was
similar in both cell types. However, c-Erb A did not activate gene
transcription through a direct repeat sequence (DR) 4 TRE in myoblasts
in contrast to results obtained in HeLa cells. Moreover, whereas
retinoic acid receptor-AP-1 interactions were functional in both cell
types, thyroid hormone receptor (T3R)-AP-1 interactions were only
functional in HeLa cells. Using electrophoretic mobility shift assays,
functional tests, and Northern blot experiments, we observed that RXR
isoforms are not expressed in proliferating myoblasts. Expression of
RXR in these cells did not influence T3R transcriptional activity
through a palindromic TRE but induced such an activity through a DR4
TRE. Moreover, it restored c-Erb A-AP-1 functionality in QM7 myoblasts
and enhanced the myogenic influence of T3. We also observed that c-Jun
overexpression in proliferating QM7 cells restored T3R transcriptional
activity through a DR4 TRE. Therefore, alternative mechanisms are
involved in the induction of T3R transcriptional activity according to
the cell status (proliferation: c-Jun; differentiation: RXR). In
addition we provide the first evidence that RXR is required to allow
inhibition of AP-1 activity by ligand-activated T3R. Lastly, we
demonstrate the importance of RXR in the regulation of myoblast
differentiation by T3.

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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
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