CTCF-Dependent Chromatin Bias Constitutes Transient Epigenetic Memory of the Mother at the H19-Igf2 Imprinting Control Region in Prospermatogonia
| Autor: | Lucy Brown, Piroska E. Szabó, Alexander Spalla, Nathan Oates, Gerd P. Pfeifer, Shirley Y. Tsai, Dong-Hoon Lee, Claudio Spalla, Tibor A. Rauch, Garrett P. Larson, Guillermo E. Rivas, Purnima Singh |
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| Rok vydání: | 2010 |
| Předmět: |
Male
CCCTC-Binding Factor Cancer Research RNA Untranslated Developmental Biology/Germ Cells Bisulfite sequencing Histones Mice Molecular Biology/DNA Methylation Genetics (clinical) Genetics Genetics and Genomics/Gene Expression Chromatin Histone DNA methylation Female RNA Long Noncoding Protein Binding Research Article lcsh:QH426-470 Genetics and Genomics/Animal Genetics Biology Methylation Models Biological Genomic Imprinting Fetus Insulin-Like Growth Factor II Genetics and Genomics/Epigenetics Animals Sulfites Epigenetics Molecular Biology/Chromatin Structure Molecular Biology Alleles Ecology Evolution Behavior and Systematics Lysine Reproducibility of Results Sequence Analysis DNA DNA Methylation Molecular Biology/Transcription Initiation and Activation Spermatogonia Repressor Proteins lcsh:Genetics Differentially methylated regions CTCF Mutation biology.protein Genomic imprinting |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 6, Iss 11, p e1001224 (2010) |
| ISSN: | 1553-7404 |
| Popis: | Genomic imprints—parental allele-specific DNA methylation marks at the differentially methylated regions (DMRs) of imprinted genes—are erased and reestablished in germ cells according to the individual's sex. Imprint establishment at paternally methylated germ line DMRs occurs in fetal male germ cells. In prospermatogonia, the two unmethylated alleles exhibit different rates of de novo methylation at the H19/Igf2 imprinting control region (ICR) depending on parental origin. We investigated the nature of this epigenetic memory using bisulfite sequencing and allele-specific ChIP–SNuPE assays. We found that the chromatin composition in fetal germ cells was biased at the ICR between the two alleles with the maternally inherited allele exhibiting more H3K4me3 and less H3K9me3 than the paternally inherited allele. We determined genetically that the chromatin bias, and also the delayed methylation establishment in the maternal allele, depended on functional CTCF insulator binding sites in the ICR. Our data suggest that, in primordial germ cells, maternally inherited allele-specific CTCF binding sets up allele-specific chromatin differences at the ICR. The erasure of these allele-specific chromatin marks is not complete before the process of de novo methylation imprint establishment begins. CTCF–dependent allele-specific chromatin composition imposes a maternal allele-specific delay on de novo methylation imprint establishment at the H19/Igf2 ICR in prospermatogonia. Author Summary Allele-specific DNA methylation is considered the primary mark that distinguishes the parental alleles of imprinted genes. Whereas allele-specific chromatin also exists at imprinted genes in the soma, this has not been assessed in the germ line. It will be important to understand what extent the chromatin composition provides clues in the germ line to the erasure and establishment of methylation imprints. Our novel methods provide the sensitivity required to answer these questions. Our results argue that the erasure of the DNA methylation imprint is complete before, and therefore does not depend on, the erasure of allele-specific chromatin marks at the H19/Igf2 imprint control region. Additionally, we show that incomplete erasure of the allele-specific chromatin is responsible for the delayed DNA methylation imprint establishment of the maternal ICR allele in prospermatogonia. The chromatin bias—the transient epigenetic memory of the mother—in fetal germ cells depends on functional CTCF insulator binding sites in this imprint control region. |
| Databáze: | OpenAIRE |
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