DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development

  title={DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development},
  author={Masaki Okano and Daphne W Bell and Daniel A. Haber and En Li},

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Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation
Findings reveal how sequence and chromatin cues guide de novo methyltransferase activity to ensure methylome integrity.
Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development
A set of unique de novo DNA methylation target sites for both DNMT3 enzymes during mammalian development that overlap with hypomethylated sites in human patients are reported.
Plasticity in Dnmt3L-dependent and -independent modes of de novo methylation in the developing mouse embryo
This study proves that the postimplantation embryo is more plastic than the germline in terms of DNA methylation mechanistic choices and, importantly, that de novo methylation can be achieved in vivo without Dnmt3L.
Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice.
It is demonstrated that Dnmt3L, a protein sharing homology with DNA methyltransferases, but lacking enzymatic activity, is essential for the establishment of maternal methylation imprints and appropriate expression of maternally imprinted genes.
Establishment and Maintenance of Genomic Methylation Patterns in Mouse Embryonic Stem Cells by Dnmt3a and Dnmt3b
It is demonstrated that genomic methylation patterns are determined partly through differential expression of different Dnmt3a and DNmt3b isoforms, and that hypermethylation of genomic DNA by Dn MT3b is necessary for ES cells to form teratomas in nude mice.
Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells
The results indicate a regulatory role for Np95, DnMT3a and Dnmt3b in mediating epigenetic silencing through histone modification followed by DNA methylation.
Ontogeny of CpG island methylation and specificity of DNMT3 methyltransferases during embryonic development in the mouse
It is revealed that the DNMT3 de novo methyltransferases play both redundant and specific functions in the establishment of DNA methylation in the mouse embryo.
Cooperativity between DNA Methyltransferases in the Maintenance Methylation of Repetitive Elements
It is concluded that ongoing de novo methylation by DnMT3a and/or Dnmt3b compensates for inefficient maintenancemethylation byDnmt1 of these endogenous repetitive sequences.
Synergistic Function of DNA Methyltransferases Dnmt3a and Dnmt3b in the Methylation of Oct4 and Nanog
The results suggest that Dnmt3a and DnMT3b form a complex through direct contact in living cells and cooperate in the methylation of the promoters of Oct4 and Nanog during cell differentiation.


Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells.
It is shown that endogenous virus was fully methylated in Dnmt2 -deficient mutant ES cells and newly integrated retrovirus DNA was methylated de novo in infected mutantES cells as efficiently as in wild-type cells.
The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors.
Investigation of the expression of human DNMT1, 3a and 3b found widespread, coordinate expression of all three transcripts in most normal tissues, and several novel alternatively spliced forms of DNMT3b, which may have altered enzymatic activity, were found to be expressed in a tissue-specific manner.
Cloning, expression and chromosome locations of the human DNMT3 gene family.
DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe.
Data suggest that any sequence-specific de novo methylation mediated by Dnmt1 is either under the control of regulatory factors that interact with DnMT1, or is cued by alternative secondary structures in DNA.
De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells.
A null mutation of the only known mammalian DNA methyltransferase gene is generated in mouse embryonic stem cells and it is found that the development of the homozygous embryos is arrested prior to the 8-somite stage, suggesting the existence of a second DNA methyl transferase in mammalian cells.
Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development.
Stage- and tissue-specific global demethylation and remethylation occurring during embryonic development are shown and it is proposed that much of the methylation observed in somatic tissues acts to stabilize and reinforce prior events that regulate the activity of specific genes, chromosome domains or the X chromosome.
Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line.
The results form a basis for the understanding of the biochemical mechanisms and role of DNA methylation in embryonic development.
Differences in DNA methylation during oogenesis and spermatogenesis and their persistence during early embryogenesis in the mouse.
Gametic differences in DNA methylation observed here indicate that methylation could provide a mechanism for imprinting maternal and paternal genomes resulting in differential regulation of parental genomes during early development.
Germ-line passage is required for establishment of methylation and expression patterns of imprinted but not of nonimprinted genes.
Results are consistent with the presence of distinct de novo DNA methyltransferase activities during oogenesis and spermatogenesis, which specifically recognize imprinted genes but are absent in the postimplantation embryo and in ES cells.
DNA methylation and chromatin modification.
  • H. Ng, A. Bird
  • Biology, Chemistry
    Current opinion in genetics & development
  • 1999