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Dnmt3L and the Establishment of Maternal Genomic Imprints

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Science  21 Dec 2001:
Vol. 294, Issue 5551, pp. 2536-2539
DOI: 10.1126/science.1065848

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Abstract

Complementary sets of genes are epigenetically silenced in male and female gametes in a process termed genomic imprinting. TheDnmt3L gene is expressed during gametogenesis at stages where genomic imprints are established. Targeted disruption ofDnmt3L caused azoospermia in homozygous males, and heterozygous progeny of homozygous females died before midgestation. Bisulfite genomic sequencing of DNA from oocytes and embryos showed that removal of Dnmt3L prevented methylation of sequences that are normally maternally methylated. The defect was specific to imprinted regions, and global genome methylation levels were not affected. Lack of maternal methylation imprints in heterozygous embryos derived from homozygous mutant oocytes caused biallelic expression of genes that are normally expressed only from the allele of paternal origin. The key catalytic motifs characteristic of DNA cytosine methyltransferases have been lost from Dnmt3L, and the protein is more likely to act as a regulator of imprint establishment than as a DNA methyltransferase.

  • * Present address: Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.

  • Present address: Department of Biological Sciences, Dartmouth College, Hanover, NH, USA.

  • To whom correspondence should be addressed. E-mail: thb12{at}columbia.edu

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