title: Inhibition of maintenance DNA methylation by Stella.
abstract: DNA methylation is a key epigenetic regulator in mammals, and the dynamic balance between methylation and demethylation impacts various processes, from development to disease. DNA methylation is erased during replication when DNA methyltransferase 1 (DNMT1) fails to methylate the daughter strand, in a process known as passive DNA demethylation. We found that the enforced expression of Stella (also known as PGC7, Dppa3), a maternal factor required for the maintenance of DNA methylation in early embryos, induced global DNA demethylation in NIH3T3 cells. This demethylation was caused by the binding of Stella to Np95 (also known as Uhrf1, ICBP90) and the subsequent inhibition of DNMT1 recruitment. Considering that impaired DNA methylation profiles are associated with various developmental or disease phenomena, Stella may be a powerful tool with which to study the biological effects of global DNA hypomethylation.
authors.affiliation: Department of Pathology, Osaka University, Osaka 565-0871, Japan; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Funaki
authors.affiliation: Nagahama Institute of Bio-Science and Technology, Shiga 526-0829, Japan; JST, CREST, Saitama 332-0012, Japan. Electronic address: tnakamura@nagahama-i-bio.ac.jp.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tsunetoshi
authors.initials: T
authors.lastname: Nakatani
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Umehara
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakashima
authors.affiliation: Department of Pathology, Osaka University, Osaka 565-0871, Japan; JST, CREST, Saitama 332-0012, Japan; Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan. Electronic address: tnakano@patho.med.osaka-u.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D019175:DNA Methylation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011506:Proteins / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C466105:DPPA3 protein, human; D011506:Proteins
keywords: DNA demethylation; Dnmt1; Np95; Stella