Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Role of N-α-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting

ABSTRACT: Genomic imprinting is an allelic gene expression phenomenon primarily controlled by allele-specific DNA methylation at the imprinting control region (ICR). How allele-specific DNA methylation at ICR is regulated is largely unknown. Mammalian N-α-acetyltransferase 10 protein (Naa10p) catalyzes N-α-acetylation of nascent proteins. Mutation of human Naa10p is linked to severe developmental defects and mental retardation, including the Ogden syndrome. Here we report that Naa10-null mice display partial embryonic lethality, growth retardation, brain disorder and maternal-effect lethality, phenotypes commonly observed in defective genomic imprinting. Genome-wide analyses reveal global DNA hypomethylation and enriched dysregulation of imprinted genes in Naa10p-null embryos and ES cells. Naa10p regulates global DNA methylation by stimulating DNA methyltransferase 1 (Dnmt1) activity, while maintaining imprinted allele methylation by binding to GCXGXG and recruits Dnmt1. Clinical mutation of Naa10p disrupts its H19-ICR binding and Dnmt1 recruitment. Our study thus links Naa10p mutation-associated human diseases to defective DNA methylation and genomic imprinting.

ORGANISM(S): Mus musculus

PROVIDER: GSE83206 | GEO | 2017/09/29

SECONDARY ACCESSION(S): PRJNA325271

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Role of N-α-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting

Project description:Genomic imprinting is an allelic gene expression phenomenon primarily controlled by allele-specific DNA methylation at the imprinting control region (ICR), of which the underlying mechanism remains largely unclear. Mammalian N-α-acetyltransferase 10 protein (Naa10p) catalyzes N-α-acetylation of nascent proteins. Mutation of human Naa10p is linked to severe developmental delays. Here we report that Naa10-null mice display partial embryonic lethality, growth retardation, brain disorder and maternaleffect lethality, phenotypes commonly observed in defective genomic imprinting. Genome-wide analyses further revealed global DNA hypomethylation and enriched dysregulation of imprinted genes in Naa10p-knockout embryos and ES cells. Mechanistically, Naa10p facilitates the binding of DNA methyltransferase 1 (Dnmt1) to DNA substrates and recruits Dnmt1 to ICRs of the imprinted allele during S phase. Moreover, the clinical lethal Ogden syndrome-associated mutation of Naa10p disrupts its binding to H19-ICR and Dnmt1 recruitment. Our study thus links Naa10p mutationassociated human disease to defective DNA methylation and genomic imprinting.

2017-10-05 | GSE102224 | GEO

Reciprocal, methylation-dependent binding of Zfp57 and Gzf1 safeguards Dlk1-Dio3 imprinting during developmental reprogramming

Project description:Genomic imprinting secures parent-specific gene expression through differential DNA methylation at imprinted control regions (ICRs). However, how unmethylated alleles resist de novo methylation remains unclear. Using an allelic Dlk1-Dio3 ICR methylation reporter and genome-wide loss-of-function screening, we identify the zinc finger protein GZF1 that binds the unmethylated maternal ICR and protects it from de novo methylation via a regulatory element containing GZF1 and ZFP57 motifs that mediates mutually exclusive, methylation-dependent binding. Loss of either factor causes reciprocal imprinting failure: Gzf1 loss induces maternal allele methylation, H3K4me3 depletion, and silencing of maternal transcripts, whereas Zfp57 loss results in maternalization. Remarkably, GZF1 protects the unmethylated ICR from de novo methylation in both oocytes and embryos, and its loss leads to perinatal death consistent with paternalization of the maternal allele. Together, our findings establish a reciprocal mechanism that maintains parental epigenetic asymmetry across both imprint establishment and embryonic reprogramming.

2026-08-04 | PXD080456 | Pride

Reciprocal, methylation-dependent binding of Zfp57 and Gzf1 safeguards Dlk1-Dio3 imprinting during developmental reprogramming [GZF1]

Project description:Genomic imprinting secures parent-specific gene expression through differential DNA methylation at imprinted control regions (ICRs). However, how unmethylated imprinted alleles resist de novo methylation remains unclear. Using an allelic methylation reporter at the Dlk1-Dio3 ICR and a genome-wide loss-of-function screen, we identify that the zinc finger protein GZF1 specifically binds the unmethylated maternal ICR and protects it from de novo methylation in mouse embryonic stem cells, early development, and oocytes. We further show that this protection occurs independently of Tet-mediated demethylation. A regulatory element containing GZF1 and ZFP57 motifs mediates mutually exclusive, methylation-dependent binding. Loss of either factor causes reciprocal imprinting failure: Gzf1 loss induces maternal allele methylation, H3K4me3 depletion, and silencing of maternal transcripts, whereas Zfp57 loss erases paternal methylation, causing locus maternalization. Gzf1-null mice exhibit postnatal growth retardation, contextualizing cis-deletions of this region and illustrating how imprinting phenotypes may differ when studied through epigenetic perturbation versus genetic deletion. Together, our findings define a reciprocal mechanism by which sequence- and methylation-sensitive factors actively memorize parental epigenetic asymmetry through opposing waves of developmental reprogramming.

2026-08-09 | GSE324182 | GEO

Reciprocal, methylation-dependent binding of Zfp57 and Gzf1 safeguards Dlk1-Dio3 imprinting during developmental reprogramming [GZF1_snp]

Project description:Genomic imprinting secures parent-specific gene expression through differential DNA methylation at imprinted control regions (ICRs). However, how unmethylated imprinted alleles resist de novo methylation remains unclear. Using an allelic methylation reporter at the Dlk1-Dio3 ICR and a genome-wide loss-of-function screen, we identify that the zinc finger protein GZF1 specifically binds the unmethylated maternal ICR and protects it from de novo methylation in mouse embryonic stem cells, early development, and oocytes. We further show that this protection occurs independently of Tet-mediated demethylation. A regulatory element containing GZF1 and ZFP57 motifs mediates mutually exclusive, methylation-dependent binding. Loss of either factor causes reciprocal imprinting failure: Gzf1 loss induces maternal allele methylation, H3K4me3 depletion, and silencing of maternal transcripts, whereas Zfp57 loss erases paternal methylation, causing locus maternalization. Gzf1-null mice exhibit postnatal growth retardation, contextualizing cis-deletions of this region and illustrating how imprinting phenotypes may differ when studied through epigenetic perturbation versus genetic deletion. Together, our findings define a reciprocal mechanism by which sequence- and methylation-sensitive factors actively memorize parental epigenetic asymmetry through opposing waves of developmental reprogramming.

2026-08-09 | GSE324367 | GEO

Role of N-a-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting

Project description:We report that Naa10-null mice display partial embryonic lethality, growth retardation, brain disorder and maternal-effect lethality, phenotypes commonly observed in defective genomic imprinting. Genome-wide analyses further reveal enriched dysregulation of imprinted genes in Naa10p-knockout ES cells.

2017-10-05 | GSE89055 | GEO

Reciprocal, methylation-dependent binding of Zfp57 and Gzf1 safeguards Dlk1-Dio3 imprinting during developmental reprogramming [CUT&Tag]

2026-08-09 | GSE337303 | GEO

Reciprocal, methylation-dependent binding of Zfp57 and Gzf1 safeguards Dlk1-Dio3 imprinting during developmental reprogramming [bulk RNAseq]

2026-08-09 | GSE337302 | GEO

Reciprocal, methylation-dependent binding of Zfp57 and Gzf1 safeguards Dlk1-Dio3 imprinting during developmental reprogramming [ChIP-seq]

2026-08-09 | GSE337143 | GEO