Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci

Diane Lees Murdock, GA McLoughlin, JR McDaid, LM Quinn, A O'Doherty, L Hiripi, Catherine Hack, CP Walsh

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Abstract

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 I 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. (C) 2004 Elsevier Inc. All rights reserved.
LanguageEnglish
Pages193-204
JournalGenomics
Volume84
Issue number1
DOIs
Publication statusPublished - Jul 2004

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Pseudogenes
Methyltransferases
Rodentia
DNA
Genes
Polyadenylation
3' Untranslated Regions
Oocytes
DNA (Cytosine-5-)-Methyltransferase
Poly A
Germ Cells
Exons
Immunohistochemistry
Polymerase Chain Reaction

Cite this

Lees Murdock, Diane ; McLoughlin, GA ; McDaid, JR ; Quinn, LM ; O'Doherty, A ; Hiripi, L ; Hack, Catherine ; Walsh, CP. / Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci. 2004 ; Vol. 84, No. 1. pp. 193-204.
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Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci. / Lees Murdock, Diane; McLoughlin, GA; McDaid, JR; Quinn, LM; O'Doherty, A; Hiripi, L; Hack, Catherine; Walsh, CP.

Vol. 84, No. 1, 07.2004, p. 193-204.

Research output: Contribution to journalArticle

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AB - 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 I 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. (C) 2004 Elsevier Inc. All rights reserved.

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