title: The Histone Acetyltransferase MOF Promotes Induces Generation of Pluripotent Stem Cells.
abstract: Histone modification plays an important role in maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). The histone acetyltransferase MOF is a key regulator of ESCs; however, the role of MOF in the process of reprogramming back to induced pluripotent stem cells (iPSCs) remains unclear. In this study, we investigated the function of MOF on the generation of iPSCs. We show that iPSCs contain high levels of MOF mRNA, and the expression level of MOF protein is dramatically upregulated following reprogramming. Most importantly, overexpression of MOF improves reprogramming efficiency and facilitates the formation of iPSCs, whereas small hairpin RNA (shRNA)-mediated knockdown of MOF impairs iPSCs generation during reprogramming. Further investigation reveals that MOF interacts with the H3K4 methyltransferase Wdr5 to promote endogenous Oct4 expression during the reprogramming process. Knockdown of MOF reduces H4K16ac and H3K4me3 modification at the Oct4 promoter. In conclusion, our data indicate that MOF is an important epigenetic regulator that is critical for efficient reprogramming.
authors.affiliation: 1 Department of Central Laboratory, China-Japan Union Hospital, Jilin University , Changchun, China .
authors.forename: Xupeng
authors.initials: X
authors.lastname: Mu
authors.affiliation: 2 Department of Biological Engineering, College of Pharmacy, Jilin University , Changchun 130033, China .
authors.forename: Shaohua
authors.initials: S
authors.lastname: Yan
authors.affiliation: 2 Department of Biological Engineering, College of Pharmacy, Jilin University , Changchun 130033, China .
authors.forename: Changhao
authors.initials: C
authors.lastname: Fu
authors.affiliation: 2 Department of Biological Engineering, College of Pharmacy, Jilin University , Changchun 130033, China .
authors.forename: Anhui
authors.initials: A
authors.lastname: Wei
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000502:physiology; D051548:Histone Acetyltransferases / Q000235:genetics / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000201:enzymology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D015854:Up-Regulation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D050814:Octamer Transcription Factor-3; C502547:WDR5 protein, human; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human; C000622683:Kat8 protein, mouse