title: The nucleosome assembly protein TSPYL2 regulates the expression of NMDA receptor subunits GluN2A and GluN2B.
abstract: TSPYL2 is an X-linked gene encoding a nucleosome assembly protein. TSPYL2 interacts with calmodulin-associated serine/threonine kinase, which is implicated in X-linked mental retardation. As nucleosome assembly and chromatin remodeling are important in transcriptional regulation and neuronal function, we addressed the importance of TSPYL2 through analyzing Tspyl2 loss-of-function mice. We detected down-regulation of N-methyl-D-aspartate receptor subunits 2A and 2B (GluN2A and GluN2B) in the mutant hippocampus. Evidence from luciferase reporter assays and chromatin immunoprecipitation supported that TSPYL2 regulated the expression of Grin2a and Grin2b, the genes encoding GluN2A and GluN2B. We also detected an interaction between TSPYL2 and CBP, indicating that TSPYL2 may activate gene expression through binding CBP. In terms of functional outcome, Tspyl2 loss-of-function impaired long-term potentiation at hippocampal Schaffer collateral-CA1 synapses. Moreover, mutant mice showed a deficit in fear learning and memory. We conclude that TSPYL2 contributes to cognitive variability through regulating the expression of Grin2a and Grin2b.
authors.affiliation: 1] Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [2] Centre for Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Ka Hing
authors.initials: KH
authors.lastname: Tsang
authors.affiliation: 1] Department of Physiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [2] Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Suk King
authors.initials: SK
authors.lastname: Lai
authors.affiliation: 1] Centre for Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [2] Department of Psychiatry, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Wing Ho
authors.initials: WH
authors.lastname: Yung
authors.affiliation: 1] Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [2] Centre for Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Liu
authors.affiliation: 1] Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [2] Centre for Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Priscilla Hoi Shan
authors.initials: PH
authors.lastname: Mak
authors.affiliation: 1] Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [2] Centre for Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Cypress Chun Pong
authors.initials: CC
authors.lastname: Ng
authors.affiliation: 1] Centre for Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [2] Department of Psychiatry, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [3] Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College London, United Kingdom.
authors.forename: Grainne
authors.initials: G
authors.lastname: McAlonan
authors.affiliation: 1] Department of Physiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [2] Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Ying Shing
authors.initials: YS
authors.lastname: Chan
authors.affiliation: 1] Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China [2] Centre for Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Siu Yuen
authors.initials: SY
authors.lastname: Chan
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins; D005239:Fear; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D007858:Learning; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D008568:Memory; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor; C432963:TSPYL2 protein, human