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postgraduate thesis: The X-encoded nucleosome assembly protein Tspyl2 regulates the expression of NMDA receptor subunits GluN2A and GluN2B

TitleThe X-encoded nucleosome assembly protein Tspyl2 regulates the expression of NMDA receptor subunits GluN2A and GluN2B
Authors
Advisors
Advisor(s):Chan, SY
Issue Date2013
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Tsang, K. [曾家慶]. (2013). The X-encoded nucleosome assembly protein Tspyl2 regulates the expression of NMDA receptor subunits GluN2A and GluN2B. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5016251
AbstractSince GluN2A and GluN2B are important in brain function, electrophysiological tests and behavioral tests were performed to study the phenotype of Tspyl2 mutant mice. Tspyl2 deficiency impaired hippocampal long-term potentiation in electrophysiological tests, indicating defects in long term plasticity. Tspyl2 mutant mice also showed defects in fear associated memory with Pavlovian fear conditioning tests but not in spatial memory with a conventional water-maze paradigm. To elucidate the signaling pathway involved, phosphorylation of downstream targets of NMDA receptors, Erk1/2 and p38 MAP kinase, was examined. Tspyl2 mutant hippocampus had a reduced level of phosphorylated p38 MAPK. These data suggested that Tspyl2 is important in brain function. Another member of NAP/SET/TSPY superfamily, Nap1l2, has been shown to regulate gene expression through promoting histone acetylation activity in neurons. To gain insight into the mechanism of how TSPYL2 regulates transcription, the effect of TSPYL2 on histone post-translational modifications was examined. H3K27Me2, a transcriptional repressive mark, was specifically increased in Tspyl2 mutant hippocampus and decreased in HEK293 cells overexpressing HA-TSPYL2. From immunocytochemistry, the staining pattern of H3K27Me2 in Tspyl2 mutant primary hippocampal neurons and HA-TSPYL2 transfected HEK293 cells was altered. These data suggested that Tspyl2 reduces the level of H3K27Me2. In conclusion, the present study shows that Tspyl2 is important in neuronal function through transcription regulation. Tspyl2 regulated the expression of Grin2a and Grin2b in hippocampal neurons. In addition, Tspyl2 reduced the di-methylation on histone H3 lysine 27 residues which is likely to affect the expression of a number of genes. Loss-of-function of Tspyl2 impaired learning and memory.
DegreeDoctor of Philosophy
SubjectMethyl aspartate - Receptors
Nucleoproteins
Dept/ProgramPaediatrics and Adolescent Medicine
Persistent Identifierhttp://hdl.handle.net/10722/224809

 

DC FieldValueLanguage
dc.contributor.advisorChan, SY-
dc.contributor.authorTsang, Ka-hing-
dc.contributor.author曾家慶-
dc.date.accessioned2016-04-15T23:15:49Z-
dc.date.available2016-04-15T23:15:49Z-
dc.date.issued2013-
dc.identifier.citationTsang, K. [曾家慶]. (2013). The X-encoded nucleosome assembly protein Tspyl2 regulates the expression of NMDA receptor subunits GluN2A and GluN2B. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5016251-
dc.identifier.urihttp://hdl.handle.net/10722/224809-
dc.description.abstractSince GluN2A and GluN2B are important in brain function, electrophysiological tests and behavioral tests were performed to study the phenotype of Tspyl2 mutant mice. Tspyl2 deficiency impaired hippocampal long-term potentiation in electrophysiological tests, indicating defects in long term plasticity. Tspyl2 mutant mice also showed defects in fear associated memory with Pavlovian fear conditioning tests but not in spatial memory with a conventional water-maze paradigm. To elucidate the signaling pathway involved, phosphorylation of downstream targets of NMDA receptors, Erk1/2 and p38 MAP kinase, was examined. Tspyl2 mutant hippocampus had a reduced level of phosphorylated p38 MAPK. These data suggested that Tspyl2 is important in brain function. Another member of NAP/SET/TSPY superfamily, Nap1l2, has been shown to regulate gene expression through promoting histone acetylation activity in neurons. To gain insight into the mechanism of how TSPYL2 regulates transcription, the effect of TSPYL2 on histone post-translational modifications was examined. H3K27Me2, a transcriptional repressive mark, was specifically increased in Tspyl2 mutant hippocampus and decreased in HEK293 cells overexpressing HA-TSPYL2. From immunocytochemistry, the staining pattern of H3K27Me2 in Tspyl2 mutant primary hippocampal neurons and HA-TSPYL2 transfected HEK293 cells was altered. These data suggested that Tspyl2 reduces the level of H3K27Me2. In conclusion, the present study shows that Tspyl2 is important in neuronal function through transcription regulation. Tspyl2 regulated the expression of Grin2a and Grin2b in hippocampal neurons. In addition, Tspyl2 reduced the di-methylation on histone H3 lysine 27 residues which is likely to affect the expression of a number of genes. Loss-of-function of Tspyl2 impaired learning and memory.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.lcshMethyl aspartate - Receptors-
dc.subject.lcshNucleoproteins-
dc.titleThe X-encoded nucleosome assembly protein Tspyl2 regulates the expression of NMDA receptor subunits GluN2A and GluN2B-
dc.typePG_Thesis-
dc.identifier.hkulb5016251-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplinePaediatrics and Adolescent Medicine-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5016251-
dc.date.hkucongregation2013-

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