Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/81144
Title: TSPYL2 regulates the expression of eZH2 target genes in neurons
Authors: Liu, H 
Peng, L
So, J
Tsang, KH
Chong, CH
Mak, PHS
Chan, KM
Chan, SY
Keywords: Nucleosome assembly protein
Epigenetics
TSPYL2
H3K27me3
EZH2
Neurons
Issue Date: 2019
Publisher: Humana Press
Source: Molecular neurobiology, Apr. 2019, v. 56, no. 4, p. 2640-2652 How to cite?
Journal: Molecular neurobiology 
Abstract: 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 that mutant neurons had an increased level of H3K27me3 in cluster 1 genes, which consist of known EZH2 target genes important in development. We detected significantly reduced expression of genes including Gbx2 and Prss16 from cluster 1 and Acvrl1, Bdnf, Egr3, Grin2c, and Igf1 from cluster 2 in the mutant. In support of a dynamic role of EZH2 in repressing marked synaptic genes, the specific EZH2 inhibitor GSK126 significantly upregulated, while the demethylase inhibitor GSKJ4 downregulated the expression of Egr3 and Grin2c. GSK126 also upregulated the expression of Bdnf in mutant primary neurons. Finally, ChIP showed that hemagglutinin-tagged TSPYL2 co-existed with EZH2 in target promoters in neuroblastoma cells. Taken together, our data suggest that TSPYL2 is recruited to promoters of specific EZH2 target genes in neurons, and enhances their expression for proper neuronal maturation and function.
URI: http://hdl.handle.net/10397/81144
ISSN: 0893-7648
EISSN: 1559-1182
DOI: 10.1007/s12035-018-1238-y
Rights: © The Author(s) 2018
Open Access This article is distributed under the terms of the Creative Commons At tribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
The following publication Liu, H., Peng, L., So, J., Tsang, K. H., Chong, C. H., Mak, P. H. S., … & Chan, S. Y. (2019). TSPYL2 regulates the expression of eZH2 target genes in neurons. Molecular neurobiology, 56(4), 2640-2652 is available at https://dx.doi.org/10.1007/s12035-018-1238-y
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