Publication Date:
2001-11-24
Description:
Complementary sets of genes are epigenetically silenced in male and female gametes in a process termed genomic imprinting. The Dnmt3L gene is expressed during gametogenesis at stages where genomic imprints are established. Targeted disruption of Dnmt3L 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bourc'his, D -- Xu, G L -- Lin, C S -- Bollman, B -- Bestor, T H -- GM59377/GM/NIGMS NIH HHS/ -- HD37687/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2536-9. Epub 2001 Nov 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Development, Transgenic Animal Facility, Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11719692" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Animals
;
Autoantigens/genetics
;
Catalytic Domain
;
Crosses, Genetic
;
DNA (Cytosine-5-)-Methyltransferase/chemistry/genetics/*physiology
;
*DNA Methylation
;
Embryo, Mammalian/cytology/*metabolism
;
Female
;
Gene Expression
;
Gene Targeting
;
*Genomic Imprinting
;
Heterozygote
;
Homozygote
;
Male
;
Mice
;
Mutation
;
Oocytes/*metabolism
;
Oogenesis
;
Phenotype
;
*Ribonucleoproteins, Small Nuclear
;
Stem Cells
;
Testis/metabolism
;
snRNP Core Proteins
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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