title: H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm.
abstract: Setd2 is known as a histone-H3K36-specific methyltransferase. However, its role in physiological function remains unclear. In this study, we show that Setd2 mainly regulates differentiation of murine embryonic stem cells (mESCs) toward primitive endoderm. Furthermore, we show that downregulated endoderm-related genes in Setd2(-/-) mESCs are associated with an aberrantly low level of Erk activity and that enforced expression of Fgfr3 can rescue the defective Erk pathway in Setd2(-/-) mESCs. Interestingly, the transcriptional initiation of Fgfr3 is directly regulated through histone H3K36me3 modification in its distal promoter region by Setd2. These results indicate that Setd2 controls the primitive endoderm differentiation of mESCs by regulating the Fgfr3-Erk signaling.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Shugao
authors.initials: S
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: National Engineering Center for Biochip at Shanghai, Shanghai 201203, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Sun
authors.affiliation: National Engineering Center for Biochip at Shanghai, Shanghai 201203, China.
authors.forename: Huasheng
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: hqh10632@rjh.com.cn.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: sjchen@stn.sh.cn.
authors.forename: Saijuan
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D004707:Endoderm / Q000166:cytology / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D013724:Teratoma / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D011495:Histone-Lysine N-Methyltransferase; C587921:SETD2 protein, mouse; C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3; D048049:Extracellular Signal-Regulated MAP Kinases