Article The Role of N-a-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting Graphical Abstract Authors Chen-Cheng Lee, Shih-Huan Peng, Genomic imprinting Li Shen, ..., Yu-Ting Yan, Yi Zhang, Paternally imprinted gene Maternally imprinted gene Li-Jung Juan ICR ICR Correspondence ICR ICR
[email protected] (Y.Z.), Naa10-KO or WT Naa10p clinical mutation:
[email protected] (L.-J.J.) S37P, V107F or R116W Dnmt1 Naa10p Naa10p Dnmt1 X In Brief X Mut X X Lee et al. reveal an unexpected function G H19 G H19 for Naa10p, which is primarily known to ICR of imprinted allele (ex: H19) ICR of imprinted allele (ex: H19) acetylate nascent peptides from ribosomes, in maintaining global DNA Methylated CpG H3K9me3/H4K20me3 methylation and marking the imprinted Unmethylated CpG H3K9Ac allele for genomic imprinting Imprinting maintenance Imprinting dysregulation maintenance. Their results suggest that Successful development Developmental defect Embryonic lethality defects in DNA methylation and genomic Growth retardation imprinting may contribute to Naa10p- Brain disorder associated Ogden syndrome. Maternal-effect lethality Highlights d Naa10p KO causes defects in genomic imprinting and embryonic development d Naa10p maintains Dnmt1 activity by facilitating Dnmt1 binding to DNA substrate d Naa10p selectively binds to ICRs of the imprinted allele via non-methylated GCXGXG d Ogden syndrome-causing Naa10p mutation disrupts ICR binding of Naa10p and Dnmt1 Lee et al., 2017, Molecular Cell 68, 1–15 October 5, 2017 ª 2017 Elsevier Inc. http://dx.doi.org/10.1016/j.molcel.2017.08.025 Please cite this article in press as: Lee et al., The Role of N-a-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting, Molecular Cell (2017), http://dx.doi.org/10.1016/j.molcel.2017.08.025 Molecular Cell Article The Role of N-a-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting Chen-Cheng Lee,1,9 Shih-Huan Peng,1,2,9 Li Shen,3,8,9 Chung-Fan Lee,1 Ting-Huei Du,1 Ming-Lun Kang,1 Guo-Liang Xu,4 Anup K.