Unknown

Dataset Information

0

The Role of N-?-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), but the underlying mechanism remains largely unclear. N-?-acetyltransferase 10 protein (Naa10p) catalyzes N-?-acetylation of nascent proteins, and mutation of human Naa10p is linked to severe developmental delays. Here we report that Naa10-null mice display partial embryonic lethality, growth retardation, brain disorders, and maternal effect 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 embryonic stem cells. Mechanistically, Naa10p facilitates binding of DNA methyltransferase 1 (Dnmt1) to DNA substrates, including the ICRs of the imprinted allele during S phase. Moreover, the lethal Ogden syndrome-associated mutation of human Naa10p disrupts its binding to the ICR of H19 and Dnmt1 recruitment. Our study thus links Naa10p mutation-associated Ogden syndrome to defective DNA methylation and genomic imprinting.

SUBMITTER: Lee CC 

PROVIDER: S-EPMC6322414 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-09-29 | GSE83206 | GEO
2017-10-05 | GSE102224 | GEO
2018-01-01 | S-EPMC5963867 | BioStudies
2017-10-05 | GSE89055 | GEO
2010-01-01 | S-EPMC2970558 | BioStudies
1000-01-01 | S-EPMC5066126 | BioStudies
2009-01-01 | S-EPMC2986258 | BioStudies
1000-01-01 | S-EPMC6027785 | BioStudies
2002-01-01 | S-EPMC133685 | BioStudies
2003-01-01 | S-EPMC196021 | BioStudies