Expression of an alternative Dnmt1 isoform during muscle differentiation.
The methylation pattern of genomic DNA undergoes dramatic changes during mammalian development, with extensive de novo methylation occurring during gametogenesis and after implantation. We identified an alternative Dnmt1 transcript in skeletal muscle by Northern blot analysis and cloned the corresponding cDNA by rapid amplification of cDNA ends and reverse transcription-PCR. Using an in vitro skeletal muscle differentiation system, we show that this alternative Dnmt1 isoform is specifically expressed in differentiated myotubes, whereas the ubiquitously expressed isoform is down-regulated during myogenesis. Sequence analysis showed that this skeletal Dnmt1 isoform is identical to the one present in testis, which had been described as untranslatable. Here we present evidence that this alternative Dnmt1 transcript present in testis and skeletal muscle is translated despite the presence of several out-of-frame upstream ATGs and gives rise to a shorter Dnmt1 isoform, which could play an active role in the change of DNA methylation patterns during gametogenesis and myogenesis.
Aguirre-Arteta
A M
AM
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Grunewald
I
I
Cardoso
M C
MC
Leonhardt
H
H
D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000502:physiology*; D019175:DNA Methylation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology
D020033:Protein Isoforms; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse