title: Nono, a Bivalent Domain Factor, Regulates Erk Signaling and Mouse Embryonic Stem Cell Pluripotency.
abstract: Nono is a component of the para-speckle, which stores and processes RNA. Mouse embryonic stem cells (mESCs) lack para-speckles, leaving the function of Nono in mESCs unclear. Here, we find that Nono functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We report that Nono loss results in robust self-renewing mESCs with epigenomic and transcriptomic features resembling the 2i (GSK and Erk inhibitors)-induced "ground state." Erk interacts with and is required for Nono localization to a subset of bivalent genes that have high levels of poised RNA polymerase. Nono loss compromises Erk activation and RNA polymerase poising at its target bivalent genes in undifferentiated mESCs, thus disrupting target gene activation and differentiation. These findings argue that Nono collaborates with Erk signaling to regulate the integrity of bivalent domains and mESC pluripotency.
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Ma
authors.affiliation: Newborn Medicine Division, Boston Children's Hospital, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Violetta
authors.initials: V
authors.lastname: Karwacki-Neisius
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Tang
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Haolin
authors.initials: H
authors.lastname: Hu
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Zhentian
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Lingchun
authors.initials: L
authors.lastname: Kong
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Ruitu
authors.initials: R
authors.lastname: Lv
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Systems Biology, Institutes of Biomedical Sciences, Fudan University, 138 Yixue Yuan Road, Shanghai 200032, China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Feizhen
authors.initials: F
authors.lastname: Wu
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Diao
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Division of Endocrinology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yujiang Geno
authors.initials: YG
authors.lastname: Shi
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: fei_lan@fudan.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Lan
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Newborn Medicine Division, Boston Children's Hospital, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: yshi@hms.harvard.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D000066673:Cell Self Renewal; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D016678:Genome; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D010766:Phosphorylation; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D016601:RNA-Binding Proteins; D059467:Transcriptome / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D000071317:Nanog Homeobox Protein; C500331:Nono protein, mouse; D016601:RNA-Binding Proteins
keywords: Erk; Neat1; Nono; RNAPII; bivalent domain; ground state; mESC; p54NRB; para-speckle; pluripotency