| First Author | Lee CC | Year | 2017 |
| Journal | Mol Cell | Volume | 68 |
| Issue | 1 | Pages | 89-103.e7 |
| PubMed ID | 28943313 | Mgi Jnum | J:251884 |
| Mgi Id | MGI:6106740 | Doi | 10.1016/j.molcel.2017.08.025 |
| Citation | Lee CC, et al. (2017) The Role of N-alpha-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting. Mol Cell 68(1):89-103.e7 |
| abstractText | 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-alpha-acetyltransferase 10 protein (Naa10p) catalyzes N-alpha-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. |
