title: ESET histone methyltransferase regulates osteoblastic differentiation of mesenchymal stem cells during postnatal bone development.
abstract: To investigate the effects of histone methyltransferase ESET (also known as SETDB1) on bone metabolism, we analyzed osteoblasts and osteoclasts in ESET knockout animals, and performed osteogenesis assays using ESET-null mesenchymal stem cells. We found that ESET deletion severely impairs osteoblast differentiation but has no effect on osteoclastogenesis, that co-transfection of ESET represses Runx2-mediated luciferase reporter while siRNA knockdown of ESET activates the luciferase reporter in mesenchymal cells, and that ESET is required for postnatal expression of Indian hedgehog protein in the growth plate. As the bone phenotype in ESET-null mice is 100% penetrant, these results support ESET as a critical regulator of osteoblast differentiation during bone development.
authors.affiliation: Department of Orthopedics and Sports Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Lawson
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Teteak
authors.forename: Jidi
authors.initials: J
authors.lastname: Gao
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jacques
authors.initials: J
authors.lastname: Hacquebord
authors.forename: Andrew
authors.initials: A
authors.lastname: Ghatan
authors.forename: Anna
authors.initials: A
authors.lastname: Zielinska-Kwiatkowska
authors.forename: Guangchun
authors.initials: G
authors.lastname: Song
authors.forename: Howard A
authors.initials: HA
authors.lastname: Chansky
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001846:Bone Development / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D034741:RNA, Small Interfering; C493716:Runx2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; C516239:SETDB1 protein, mouse
keywords: Bone development; Epigenetic regulation; Mesenchymal stem cell; Osteoblast differentiation