Visit our Expo - Redox and Inflammation signaling 2012

Session XVII : Cell signaling in health and disease Poster XVII, 16
Molecular regulation of the expression of human A#H-J-J Locus, encoding Aspartyl-#hydroxylase,
Junctin and Junctate
Giordana Feriotto1, Alessia Finotti1, Giulia Breveglieri1, Pompeo Volpe3, Susan
Treves2, Francesco Zorzato2, and Roberto Gambari1
Dept of Biochemistry and Molecular Biology1, Dept of Experimental and Diagnostic
Medicine2, Ferrara University, Italy; Dept of Biomedical Experimental Sciences3,
Padova University, Italy; E-mail: gam@unife.it
We have recently cloned and characterised the A#H-J-J locus, a genomic sequence that
generates three functionally distinct proteins, the enzyme aspartyl #-hydroxylase (A#H),
junctin, a structural protein of sarcoplasmic reticulum membrane, and the membrane-bound
protein junctate (1, 2). The expression of the A#H-J-J locus is regulated by (a) transcription
directed by the P1 and the P2 promoters (located upstream of exon 1 and exon 2 respectively),
and (b) alternative splicing. In order to functionally characterise the two promoter sequences,
we first demonstrate that mRNAs from P1 promoter are actively transcribed in all the human
tissues and cell lines analysed, while the expression directed from the P2 promoter is tissue
specific, in particular restricted to skeletal muscle, heart and brain. The P1 region responsible
for maximal transcription contains at least twelve GC-box homologous to Sp1 consensus
binding sequence; by EMSA we identified three GC-rich elements which bind Sp family
nuclear factors with high efficiency (3). On the contrary, the P2 promoter contains sequences
which bind to different transcription factors, including MEF-2 and MEF-3 (4). The
transcription directed by the P2 promoter is induced by high expression of MEF-2 and
inhibited by HDAC4. ChIP analysis showed that MEF-2 efficiently binds chromatin of the P2
promoter in C2C12 myotubes (4). In addition, we found that A#H and junctate transcripts
exhibit single or multiple exons skipping in the region coding for the Ca++ binding domain
leading to a number of A#H and junctate mRNA variants.
1. Treves S et al. (2000) J. Biol. Chem. 275, 39555; 2. Treves S et al. (2004) J. Cell. Biol.
166, 537; 3. Mischiati C et al. (1999) J. Biol. Chem. 274, 33114; 4. Feriotto G et al. (2005)
Mol. Cell. Biol. 25, 3261.
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