title: The Histone Methyltransferase Ash1l is Required for Epidermal Homeostasis in Mice.
abstract: Epidermal homeostasis under normal and healing conditions are critical for the physical and functional maintenance of the skin barrier. It requires a proper balance between keratinocyte proliferation and differentiation under genetic and epigenetic regulations. Here we show that mice carrying a hypomorphic mutation of the histone methyltransferase Ash1l [(absent, small, or homeotic)-like (Drosophila)] develop epidermal hyperplasia and impaired epidermal stratification upon aging. In adult mutants, loss of Ash1l leads to more proliferative keratinocytes in disturbed differentiation stages. After wounding, Ash1l mutation leads to delayed re-epithlialization but increased keratinocyte proliferation at the wound edge. Elevated c-Myc expression could be observed in both aged and wounded mutant tissues. Taken together, these observations revealed an important role of the epigenetic regulator Ash1l in epidermal homeostasis.
authors.affiliation: State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.|Howard Hughes Medical Institute, Department of Molecular, Cellular, Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.affiliation: State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.|Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.|Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wu
mesh_terms: D000375:Aging; D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006965:Hyperplasia / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008745:Methylation; D051379:Mice; D016296:Mutagenesis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014945:Wound Healing
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C000600280:Ash1l protein, mouse; D011495:Histone-Lysine N-Methyltransferase