A cis-acting regulatory element that affects the alternative splicing of a muscle-specific exon in the mouse NCAM gene.
The pre-mRNA encoding the neural cell adhesion molecule (NCAM) is spliced to generate NCAM isoforms containing the muscle-specific domain (MSD) during myogenesis. Utilizing chimeric NCAM minigenes, we searched for cis-acting elements that contribute to the alternative selection of exon MSDb, one of the four exons encoding MSD, and identified an intronic cis-element located downstream of exon MSDb. The cis-element acted as a negative regulator for the selection of exon MSDb in nonmuscle fibroblasts but not in myoblasts, that are already destined to differentiate into muscle cells. The suppressive effect of this cis-element on the selection of exon MSDb was released in the process of myogenesis. When MyoD was co-expressed with a minigene containing this element in fibroblasts, the suppressive effect of the cis-element was released as the cells underwent differentiation. We propose that this cis-element contributes at least as one of the regulatory elements in the differentiation state-dependent selection of MSD exons in vivo.
Kawahigashi
H
H
Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565, Japan.
Harada
Y
Y
Asano
A
A
Nakamura
M
M
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005091:Exons; D005809:Genes, Regulator; D007438:Introns; D051379:Mice; D009132:Muscles / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D017570:MyoD Protein; D019006:Neural Cell Adhesion Molecules; D004247:DNA