Afr. Stewart et al., TRANSCRIPTION FACTOR RTEF-1 MEDIATES ALPHA(1)-ADRENERGIC REACTIVATIONOF THE FETAL GENE PROGRAM IN CARDIAC MYOCYTES, Circulation research, 83(1), 1998, pp. 43-49
Citations number
46
Categorie Soggetti
Hematology,"Peripheal Vascular Diseas","Cardiac & Cardiovascular System
alpha(1)-Adrenergic receptor stimulation induces cardiac myocytes to h
ypertrophy and reactivates many fetal genes, including beta-myosin hea
vy chain (beta MyHC) and skeletal alpha-actin (SKA), by signaling thro
ugh myocyte-specific CAT (M-CAT) cis elements, binding sites of the tr
anscriptional enhancer factor-1 (TEF-1) family of transcription factor
s. To examine functional differences between TEF-1 and related to TEF-
1 (RTEF-1) in alpha(1)-adrenergic reactivation of the fetal program, e
xpression constructs were cotransfected with beta MyHC and SKA promote
r/reporter constructs in neonatal rat cardiac myocytes. TEF-1 overexpr
ession tended to transactivate a minimal beta MyHC promoter but signif
icantly interfered with a minimal SKA promoter. In contrast, RTEF-1 tr
ansactivated both the minimal beta MyHC and SKA promoters. TEF-1 and R
TEF-1 also affected the alpha(1)-adrenergic response of the beta MyHC
and SKA promoters differently. TEF-1 had no effect. In contrast, RTEF-
1 potentiated the alpha(1)-adrenergic responses of the SKA promoter an
d of a -3.3-kb beta MyHC promoter. To determine why the promoters resp
onded differently to TEF-1 and RTEF-1, promoters with mutated M-CAT el
ements were tested in the same way. The beta MyHC promoter required an
intact M-CAT element to respond to TEF-1 and RTEF-1, whereas the SKA
promoter M-CAT was required for the TEF-1 response but not for the RTE
F-1 response, suggesting that SKA promoter-specific cofactors may be i
nvolved. By competition gel shift assay, the M-CAT of the minimal beta
MyHC promoter had a lower affinity than that of the SKA promoter, whi
ch partly explains the different responses of these promoters to TEF1.
These results highlight functional differences between TEF-1 and RTEF
-1 and suggest a novel function of RTEF-1 in mediating the alpha(1)-ad
renergic response in hypertrophic cardiac myocytes.