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

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 r...

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Bibliographic Details
Published in:Developmental dynamics 2005-04, Vol.232 (4), p.992-1002
Main Authors: Lees‐Murdock, Diane J., Shovlin, Tanya C., Gardiner, Tom, De Felici, Massimo, Walsh, Colum P.
Format: Article
Language:English
Subjects:
alternative splicing
Alternative Splicing - physiology
Animals
Cell Nucleus - metabolism
DNA (Cytosine-5-)-Methyltransferases - biosynthesis
DNA Methylation
DNA methyltransferase
DNA Methyltransferase 3A
Female
Gene Expression Regulation - physiology
Male
methylation
Mice
mouse
Oocytes - cytology
Oocytes - physiology
ovary
primordial germ cells
Spermatogonia - cytology
Spermatogonia - physiology
testis
transcription
Transcription, Genetic - physiology
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Summary: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. Developmental Dynamics 232:992–1002, 2005. © 2005 Wiley‐Liss, Inc.
ISSN:1058-8388
1097-0177
DOI:10.1002/dvdy.20288