title: Myocyte enhancer factor 2 activates promoter sequences of the human AbetaH-J-J locus, encoding aspartyl-beta-hydroxylase, junctin, and junctate.
abstract: Alternative splicing of the locus AbetaH-J-J generates three functionally distinct proteins: an enzyme, AbetaH (aspartyl-beta-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 the AbetaH-J-J locus. We demonstrate that the P2 promoter of the AbetaH-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-kappaB 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 AbetaH-J-J P2 promoter is induced by high expression of MEF-2, further stimulated by calcineurin and Ca2+/calmodulin-dependent protein kinase I, and inhibited by histone deacetylase 4.
authors.affiliation: Biotechnology Center, Biology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
authors.forename: Giordana
authors.initials: G
authors.lastname: Feriotto
authors.forename: Alessia
authors.initials: A
authors.lastname: Finotti
authors.forename: Pompeo
authors.initials: P
authors.lastname: Volpe
authors.forename: Susan
authors.initials: S
authors.lastname: Treves
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Cecilia
authors.initials: C
authors.lastname: Angelelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Zorzato
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D019703:Calcineurin / Q000378:metabolism / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology; D006801:Humans; D064326:MEF2 Transcription Factors; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D018006:Myogenic Regulatory Factors; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology; D017384:Sequence Deletion; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
chemical_list: D002135:Calcium-Binding Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C408202:MEF-3 protein, human; D064326:MEF2 Transcription Factors; D008565:Membrane Proteins; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D016328:NF-kappa B; D012097:Repressor Proteins; D014157:Transcription Factors; D006899:Mixed Function Oxygenases; C419389:ASPH protein, human; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019703:Calcineurin; C400300:HDAC4 protein, human; D006655:Histone Deacetylases