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

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.
LanguageEnglish
Pages457-467
JournalHuman Reproduction
Volume22
Issue number2
DOIs
Publication statusPublished - Feb 2007

Fingerprint

Germ Cells
Oocytes
Introns
Methylation
Testis
Ribonuclease H
Messenger RNA
Spermatocytes
Methyltransferases
Regulator Genes
Northern Blotting
Open Reading Frames
Genes
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Ovary
Complementary DNA
Polymerase Chain Reaction
DNA
Proteins

Cite this

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
Shovlin, T. C. ; Bourc'his, D. ; La Salle, S. ; O'Doherty, A. ; Trasler, J. M. ; Bestor, T. H. ; Walsh, Colum. / Sex-specific promoters regulate Dnmt3L expression in mouse germ cells. In: Human Reproduction. 2007 ; Vol. 22, No. 2. pp. 457-467.
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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.",
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Shovlin, TC, Bourc'his, D, La Salle, S, O'Doherty, A, Trasler, JM, Bestor, TH & Walsh, C 2007, 'Sex-specific promoters regulate Dnmt3L expression in mouse germ cells', Human Reproduction, vol. 22, no. 2, pp. 457-467. https://doi.org/10.1093/humrep/de1379

Sex-specific promoters regulate Dnmt3L expression in mouse germ cells. / Shovlin, T. C.; Bourc'his, D.; La Salle, S.; O'Doherty, A.; Trasler, J. M.; Bestor, T. H.; Walsh, Colum.

In: Human Reproduction, Vol. 22, No. 2, 02.2007, p. 457-467.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sex-specific promoters regulate Dnmt3L expression in mouse germ cells

AU - Shovlin, T. C.

AU - Bourc'his, D.

AU - La Salle, S.

AU - O'Doherty, A.

AU - Trasler, J. M.

AU - Bestor, T. H.

AU - Walsh, Colum

PY - 2007/2

Y1 - 2007/2

N2 - 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.

AB - 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.

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DO - 10.1093/humrep/de1379

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VL - 22

SP - 457

EP - 467

JO - Human Reproduction

T2 - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 2

ER -

Shovlin TC, Bourc'his D, La Salle S, O'Doherty A, Trasler JM, Bestor TH et al. Sex-specific promoters regulate Dnmt3L expression in mouse germ cells. Human Reproduction. 2007 Feb;22(2):457-467. https://doi.org/10.1093/humrep/de1379