Myocyte enhancer factor 2 activates promoter sequences of the human AbetaH-J-J locus, encoding aspartyl-beta-hydroxylase, junctin, and junctate

Giordana Feriotto, Alessia Finotti, Pompeo Volpe, Susan Treves, Stefano Ferrari, Cecilia Angelelli, Francesco Zorzato, Roberto Gambari
Alternative splicing of the locus A␤H-J-J generates three functionally distinct proteins: an enzyme, A␤H (aspartyl-␤-hydroxylase), a structural protein of the sarcoplasmic reticulum membrane (junctin), and an integral membrane calcium binding protein (junctate). Junctin and junctate are two important proteins involved in calcium regulation in eukaryotic cells. To understand the regulation of these two proteins, we identified and functionally characterized one of the two promoter sequences of
more » ... A␤H-J-J locus. We demonstrate that the P2 promoter of the A␤H-J-J locus contains (i) a minimal sequence localized within a region ؊159 bp from the transcription initiation site, which is sufficient to activate transcription of both mRNAs; (ii) sequences which bind known transcriptional factors such as those belonging to the myocyte enhancer factor 2 (MEF-2), MEF-3, and NF-B protein families; and (iii) sequences bound by unknown proteins. The functional characterization of the minimal promoter in C2C12 cells and in the rat soleus muscle in vivo model indicates the existence of cis elements having positive and negative effects on transcription. In addition, our data demonstrate that in striated muscle cells the calcium-dependent transcription factor MEF-2 is crucial for the transcription activity directed by the P2 promoter. The transcription directed by the A␤H-J-J P2 promoter is induced by high expression of MEF-2, further stimulated by calcineurin and Ca2 ؉ /calmodulindependent protein kinase I, and inhibited by histone deacetylase 4.
doi:10.5451/unibas-ep29466 fatcat:nni6lwqwe5fa3dhocwuzw5jzxi