Human Molecular Genetics, Vol 7, 2103-2112, Copyright © 1998 by Oxford University Press
Y Murakami, H Ohto, U Ikeda, K Shimada, T Momoi and K Kawakami
We analyzed the expression of mouse DMAHP / Six5 (the myotonic
dystrophy-associated homeodomain protein gene) during embryogenesis and in
various tissues by northern blotting. Expression was observed as early as
embryonic day 7 (E7) and continued to E17. Abundant expression was observed
in neonatal heart and skeletal muscle with potential links to the phenotype
of myotonic dystrophy. The transcription initiation sites of the gene were
analyzed in mouse E11 and E15 embryos and in adult skeletal and heart
muscle. Three major transcription initiation sites were identified, the
proximal site was specific to the early E11 embryo, while the other two
were common among the heart and skeletal muscle and E11 and E15 embryos.
All transcription initiation sites were downstream of the corresponding CTG
repeat locus of the mouse gene (- 1195), excluding a possible inclusion of
the CUG repeat sequence in mRNA leading to abnormal splicing or to
translation of aberrant protein. For analysis of the regulatory elements in
the promoter region, we used P19 embryonal carcinoma cells which abundantly
express mouse DMAHP / Six5. Multiple positive and negative elements were
identified in the promoter region. All positive elements were Sp1/Sp3
binding sites and one of the negative elements was a novel factor binding
site. The transcription initiation sites and regulatory elements are
conserved between human and mouse DMAHP.
ARTICLES
Promoter of mDMAHP/Six5: differential utilization of multiple transcription initiation sites and positive/negative regulatory elements
Department of Biology and Department of Cardiology, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
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