DNA methyltransferase expression in the mouse germ line during periods of de novo methylation

D. J. Lees-Murdock, T. C. Shovlin, T. Gardiner, M. De Felici, C. P. Walsh

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

DNA methyltransferase (DNMT) 3A and DNMT3B are both active de novo DNA methyltransferases required for development, whereas DNMT3L, which has no demonstrable methyltransferase activity, is required for methylation of imprinted genes in the oocyte. We show here that different mechanisms are used to restrict access by these proteins to their targets during germ cell development. Transcriptional control of the Dnmt3l promoter guarantees that message is low or absent except during periods of de novo activity. Use of an alternative promoter at the Dnmt3a locus produces the shorter Dnmt3a2 transcript in the germ line and postimplantation embryo only, whereas alternative splicing of the Dnmt3b transcript ensures that Dnmt3b1 is absent in the male prospermatogonia. Control of subcellular protein localization is a common theme for DNMT3A and DNMT3B, as proteins were seen in the nucleus only when methylation was occurring. These mechanisms converge to ensure that the only time that functional products from each locus are present in the germ cell nuclei is around embryonic day 17.5 in males and after birth in the growing oocytes in females.
Original languageUndefined/Unknown
Pages (from-to)992-1002
Number of pages11
JournalDevelopmental dynamics : an official publication of the American Association of Anatomists
Volume232
Issue number4
Publication statusPublished - 01 Apr 2005

Bibliographical note

LR: 20061115; CI: Copyright 2005; JID: 9201927; EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase); EC 2.1.1.37 (DNA methyltransferase 3A); ppublish

Keywords

  • Alternative Splicing/physiology
  • Animals
  • Cell Nucleus/metabolism
  • DNA (Cytosine-5-)-Methyltransferase/biosynthesis
  • DNA Methylation
  • Female
  • Gene Expression Regulation/physiology
  • Male
  • Mice
  • Oocytes/cytology/physiology
  • Spermatogonia/cytology/physiology
  • Transcription, Genetic/physiology

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