Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci.
DNA (cytosine-5-)-methyltransferase genes are important for normal development in mice and humans. We describe here 11 pseudogenes spread among human, mouse, and rat belonging to this gene family, ranging from 1 pseudogene in humans to 7 in rat, all belonging to the Dnmt3 subfamily. All except 1 rat Dnmt3b pseudogene appear to be transcriptionally silent. Dnmt3a2, a transcript variant of Dnmt3a starting at an alternative promoter, had the highest number of processed pseudogenes, while none were found for the canonical Dnmt3a, suggesting the former transcript is more highly expressed in germ cells. Comparison of human, mouse, and rat Dnmt3a2 sequences also suggests that human exon 8 is a recent acquisition. Alignment of the 3'UTR of Dnmt3a2 among the functional genes and the processed pseudogenes suggested that a second polyadenylation site downstream of the RefSeq poly(A) was being used in mice, resulting in a longer 3'UTR, a finding confirmed by RT-PCR in mouse tissues. We also found conserved cytoplasmic polyadenylation elements, usually implicated in regulating translation in oocytes, in Dnmt3b and Dnmt1. Expression of DNMT3B in the mouse oocyte was confirmed by immunocytochemistry. These results clarify the structure of a number of loci in the three species examined and provide some useful insights into the structure and evolution of this gene family.
Lees-Murdock
Diane J
DJ
Cancer and Ageing Research Group, UK.
McLoughlin
Gerard A
GA
McDaid
Jennifer R
JR
Quinn
Lisa M
LM
O'Doherty
Alan
A
Hiripi
László
L
Hack
Catherine J
CJ
Walsh
Colum P
CP
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D005810:Multigene Family / Q000235:genetics*; D009865:Oocytes / Q000378:metabolism; D011544:Pseudogenes / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D039104:RNA 3' Polyadenylation Signals / Q000235:genetics*; D051381:Rats; D014158:Transcription, Genetic / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
D020413:3' Untranslated Regions; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000097584:DNA Methyltransferase 3B; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; C000619382:Dnmt1 protein, rat