Multiple levels of control of the expression of the human A beta H-J-J locus encoding aspartyl-beta-hydroxylase, junctin, and junctate.
The human AbetaH-J-J locus is a genomic sequence which generates three functionally distinct proteins, the enzyme aspartyl-beta-hydroxylase (AbetaH), the structural protein of sarcoplasmic reticulum junctin, and the membrane-bound calcium binding protein junctate. The first and second exons are mutually exclusive when mature mRNAs are produced. Moreover, the use of different splice donors has been shown to be involved in the generation of protein diversity by alternative splicing. As to transcriptional regulation, two promoters (P1 and P2) were identified. When the P1 and P2 promoter sequences are compared, important differences are clearly detectable. The most interesting result emerging from studies focused on the P2 promoter is that the calcium-dependent transcriptional factor MEF-2 activates the transcription of junctin, junctate, and AbetaH in excitable tissues and, to a lesser extent, in kidney. No Sp1 binding sites are present in the P2 promoter. In contrast, P1 promoter contains GC-rich sequences, which have homologies with the Sp1 consensus binding site.
Feriotto
Giordana
G
Department of Biochemistry and Molecular Biology, Section of Molecular Biology, Via Fossato di Mortara 74, 44100 Ferrara, Italy.
Finotti
Alessia
A
Breveglieri
Giulia
G
Treves
Susan
S
Zorzato
Francesco
F
Gambari
Roberto
R
D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*
D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D006899:Mixed Function Oxygenases; C058291:aspartic acid 2-oxoglutarate-dependent dioxygenase; C419389:ASPH protein, human