biostudies-literatureLiu HResearch Grants Council of the Hong Kong Special Administrative Region, ChinaEdward Sai Kim Hotung Paediatric Education and Research Fund2640-2652https://www.ebi.ac.uk/biostudies/studies/S-EPMC6459796biostudies-literatureUnknown56(4)Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. We have previously shown that Tspyl2 knockout mice had impaired learning and sensorimotor gating, and TSPYL2 facilitates the expression of Grin2a and Grin2b through interaction with CREB-binding protein. To identify other genes regulated by TSPYL2, here, we showed that Tspyl2 knockout mice had an increased level of H3K27 trimethylation (H3K27me3) in the hippocampus, and TSPYL2 interacted with the H3K27 methyltransferase enhancer of zeste 2 (EZH2). We performed chromatin immunoprecipitation (ChIP)-sequencing in primary hippocampal neurons and divided all Refseq genes by k-mean clustering into four clusters from highest level of H3K27me3 to unmarked. We confirmed thatMolecular neurobiologyTSPYL2 Regulates the Expression of EZH2 Target Genes in Neurons.PMC645979617102014Liu HTsang KHSo JChan KMChan SYMak PHSPeng LChong CHfalseTSPYL2 Regulates the Expression of EZH2 Target Genes in Neurons.Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. We have previously shown that Tspyl2 knockout mice had impaired learning and sensorimotor gating, and TSPYL2 facilitates the expression of Grin2a and Grin2b through interaction with CREB-binding protein. To identify other genes regulated by TSPYL2, here, we showed that Tspyl2 knockout mice had an increased level of H3K27 trimethylation (H3K27me3) in the hippocampus, and TSPYL2 interacted with the H3K27 methyltransferase enhancer of zeste 2 (EZH2). We performed chromatin immunoprecipitation (ChIP)-sequencing in primary hippocampal neurons and divided all Refseq genes by k-mean clustering into four clusters from highest level of H3K27me3 to unmarked. We confirmed that2019-01-01T00:00:00Z2019 Apr2026-04-07T20:23:06.245Z2019-06-06T23:05:35ZS-EPMC64597963005135210.1007/s12035-018-1238-y