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

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<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>Dnmt3l</jats:italic> promoter guarantees that message is low or absent except during periods of de novo activity. Use of an alternative promoter at the <jats:italic>Dnmt3a</jats:italic> locus produces the shorter <jats:italic>Dnmt3a2</jats:italic> transcript in the germ line and postimplantation embryo only, whereas alternative splicing of the <jats:italic>Dnmt3b</jats:italic> transcript ensures that <jats:italic>Dnmt3b1</jats:italic> 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.</jats:p>

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