Sex-specific promoters regulate Dnmt3L expression in mouse germ cells

T. C. Shovlin, D. Bourc'his, S. La Salle, A. O'Doherty, J. M. Trasler, T. H. Bestor, Colum Walsh

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Abstract

BACKGROUND: Dnmt3L, a member of the DNA methyltransferase 3 family, lacks enzymatic activity but is required for de-novo methylation of imprinted genes in oocytes and for transposon repression in male germ cells. METHODS: We used northern blots, RT-PCR, 5' rapid amplification of complementary DNA (cDNA) ends (RACE), RNase H mapping, real-time/quantitative RT-PCR and in situ hybridization to identify and characterize Dnmt3L transcripts produced during germ cell development. RESULTS: Mouse Dnmt3L uses three sex-specific promoters, not the single promoter previously thought. A promoter active in prospermatogonia drives transcription of an mRNA encoding the full-length protein in perinatal testis, where de-novo methylation occurs. Late pachytene spermatocytes activate a second promoter in intron 9 of the Dnmt3L gene. After this stage, the predominant transcripts are three truncated mRNAs, which appear to be non-coding. We could also detect similar adult testis transcripts in humans. In the mouse ovary, an oocyte-specific promoter located in an intron of the neighbouring autoimmune regulator (Aire) gene produces a transcript with the full open reading frame (ORF). This is the only Dnmt3L transcript found in growing oocytes and is absent in the oocytes of Dnmt3L-/- females. CONCLUSIONS: Sex-specific promoters control Dnmt3L expression in the mouse germ line, mirroring the situation at the Dnmt1 and Dnmt3A loci.
Original languageEnglish
Pages (from-to)457-467
JournalHuman Reproduction
Volume22
Issue number2
DOIs
Publication statusPublished - Feb 2007

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Shovlin, T. C., Bourc'his, D., La Salle, S., O'Doherty, A., Trasler, J. M., Bestor, T. H., & Walsh, C. (2007). Sex-specific promoters regulate Dnmt3L expression in mouse germ cells. Human Reproduction, 22(2), 457-467. https://doi.org/10.1093/humrep/de1379