PittsburghV1, Main, Merge, bibRecord, 000F40

The Dnmt1 Intrinsically Disordered Domain Regulates Genomic Methylation During Development

Identifieur interne : 000F40 ( Main/Merge ); précédent : 000F39; suivant : 000F41

The Dnmt1 Intrinsically Disordered Domain Regulates Genomic Methylation During Development

Auteurs : Ben Shaffer [États-Unis] ; Serge Mcgraw [Canada] ; Siyu C. Xiao [États-Unis] ; Donovan Chan [Canada] ; Jacquetta Trasler [Canada] ; J. Richard Chaillet [États-Unis]

Source :

Genetics [ 0016-6731 ] ; 2014.

RBID : PMC:4317660

Descripteurs français

English descriptors

KwdEn :
- Amino Acid Sequence, Animals, Cell Line, DNA (Cytosine-5-)-Methyltransferase (chemistry), DNA (Cytosine-5-)-Methyltransferase (genetics), DNA (Cytosine-5-)-Methyltransferase (metabolism), DNA Methylation, Embryonic Stem Cells (metabolism), Exons, Female, Gene Expression Regulation, Developmental, Genetic Association Studies, Genome, Genome-Wide Association Study, Intrinsically Disordered Proteins, Male, Mice, Molecular Sequence Data, Mutation, Phenotype, Protein Interaction Domains and Motifs, Sequence Alignment.
MESH :
- chemical , chemistry : DNA (Cytosine-5-)-Methyltransferase.
- chemical , genetics : DNA (Cytosine-5-)-Methyltransferase.
- chemical , metabolism : DNA (Cytosine-5-)-Methyltransferase.
- metabolism : Embryonic Stem Cells.
- Amino Acid Sequence, Animals, Cell Line, DNA Methylation, Exons, Female, Gene Expression Regulation, Developmental, Genetic Association Studies, Genome, Genome-Wide Association Study, Intrinsically Disordered Proteins, Male, Mice, Molecular Sequence Data, Mutation, Phenotype, Protein Interaction Domains and Motifs, Sequence Alignment.

Abstract

The DNMT1 cytosine methyltransferase enzyme contains a large ∼300-aa intrinsically disordered domain (IDD) that we previously showed regulated DNA methylation patterns in mouse ES cells. Here we generated seven mouse lines with different mutations in the IDD. Homozygous mutant mice of five lines developed normally, with normal levels of methylation on both imprinted and nonimprinted DNA sequences. The other two lines, however, had alterations in imprinted and/or nonimprinted (global) DNA methylation appearing during embryonic development. Embryos of one line expressing a DNMT1 variant containing a 6-aa rat orthologous sequence in the IDD maintained imprinted methylation, showed very reduced levels of global methylation and occasionally completed fetal development. These in vivo studies demonstrate that at least two DNMT1-dependent methylation processes can be distinguished during fetal development. One process maintains the bulk of genomic methylation on nonimprinted sequences. The other process maintains methylation on a much smaller class of sequences including but not limited to gametic differentially methylated domains (gDMDs) that transmit essential imprinted parent-specific methylation for embryonic development.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317660

DOI: 10.1534/genetics.114.173609
PubMed: 25533200
PubMed Central: 4317660

Links to Exploration step

PMC:4317660

Le document en format XML

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<front><div type="abstract" xml:lang="en"><p>The DNMT1 cytosine methyltransferase enzyme contains a large ∼300-aa intrinsically disordered domain (IDD) that we previously showed regulated DNA methylation patterns in mouse ES cells. Here we generated seven mouse lines with different mutations in the IDD. Homozygous mutant mice of five lines developed normally, with normal levels of methylation on both imprinted and nonimprinted DNA sequences. The other two lines, however, had alterations in imprinted and/or nonimprinted (global) DNA methylation appearing during embryonic development. Embryos of one line expressing a DNMT1 variant containing a 6-aa rat orthologous sequence in the IDD maintained imprinted methylation, showed very reduced levels of global methylation and occasionally completed fetal development. These <italic>in vivo</italic>
 studies demonstrate that at least two DNMT1-dependent methylation processes can be distinguished during fetal development. One process maintains the bulk of genomic methylation on nonimprinted sequences. The other process maintains methylation on a much smaller class of sequences including but not limited to gametic differentially methylated domains (gDMDs) that transmit essential imprinted parent-specific methylation for embryonic development.</p>
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The Dnmt1 Intrinsically Disordered Domain Regulates Genomic Methylation During Development

The Dnmt1 Intrinsically Disordered Domain Regulates Genomic Methylation During Development

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Descripteurs français

English descriptors

Abstract

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Links to Exploration step

Le document en format XML

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