Sex-specific exons control DNA methyltransferase in mammalian germ cells.
The spermatozoon and oocyte genomes bear sex-specific methylation patterns that are established during gametogenesis and are required for the allele-specific expression of imprinted genes in somatic tissues. The mRNA for Dnmt1, the predominant maintenance and de novo DNA (cytosine-5)-methyl transferase in mammals, is present at high levels in postmitotic murine germ cells but undergoes alternative splicing of sex-specific 5' exons, which controls the production and localization of enzyme during specific stages of gametogenesis. An oocyte-specific 5' exon is associated with the production of very large amounts of active Dnmt1 protein, which is truncated at the N terminus and sequestered in the cytoplasm during the later stages of oocyte growth, while a spermatocyte-specific 5' exon interferes with translation and prevents production of Dnmt1 during the prolonged crossing-over stage of male meiosis. During the course of postnatal oogenesis, Dnmt1 is present at high levels in nuclei only in growing dictyate oocytes, a stage during which gynogenetic developmental potential is lost and biparental developmental potential is gained.
Mertineit
C
C
Department of Genetics and Development, College of Physicians and Surgeons at Columbia University, New York, NY 10032, USA.
Yoder
J A
JA
Taketo
T
T
Laird
D W
DW
Trasler
J M
JM
Bestor
T H
TH
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D003593:Cytoplasm / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000201:enzymology*; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000201:enzymology*
D017931:DNA Primers; D012333:RNA, Messenger; D004248:DNA (Cytosine-5-)-Methyltransferases