EZH1 is an antipsychotic-sensitive epigenetic modulator of social and motivational behavior that is dysregulated in schizophrenia

Differential brain ADRA2A and ADRA2C gene expression and epigenetic regulation in schizophrenia. Effect of antipsychotic drug treatment

“…The relevance of histone methylation processes was already put forward in the GWAS study from the Psychiatric Genomics Consortium [ 56 ], whereby histone methylation showed the strongest association with psychiatric disorders. Moreover, H3K27 methyltransferase EZH1 expression has been reported to be increased in PFC of schizophrenia subjects [ 18 ]. With our methodology, we cannot assure that regulation of ADRA2A promoter by H3K4me3 and H3K27me3 occur at the same cell.…”

“…According to our results, histone PTMs at ADRA2A and ADRA2C promoters are influenced by sex, ST, and PMD of the samples. Actually, the effect of sex on epigenetics has been previously described [ 71 ] with evidence for HDAC and HMT sex-specific expression [ 18 , 28 , 72 ]. In this sense, our study found that all histone PTMs affected by sex of the subjects showed increased values for females.…”

“…Several evidence suggests that histone PTMs contribute to the development of schizophrenia. Some of these findings are: altered expression of various enzymes, such as increased expression of histone methyltransferases (HMT) [ 18 – 20 ], histone deacetylase 1 (HDAC1) [ 21 , 22 ], and reduced expression of HDAC2 [ 23 , 24 ] in prefrontal cortex (PFC) of schizophrenia subjects. Studies of chromatin immunoprecipitation followed by sequencing (ChIP-Seq) in human brain have found an overrepresentation of open chromatin-associated modifications [histone H3 lysine 4 trimethylation (H3K4me3 and histone H3 lysine 27 acetylation (H3K27ac)] in schizophrenia-related genes, this finding being specific for neuronal cells [ 25 ].…”

Ezh1 regulates expression of <i>Cpg15/Neuritin</i> in mouse cortical neurons

“…Although Ezh1 regulates the expression of PSD95 and binds to the Psd95 promoter in the rat hippocampus (18), no other reports on target of Ezh1 have been reported in the nervous system. Ezh1 is enriched in the adult mouse brain, and knockdown of Ezh1 in the mouse prefrontal cortex attenuates sociability and promotes motivational behaviors (28). However, the molecular mechanisms responsible for these behavior phenotypes are not fully understood.…”

“…In mature MSNs, PRC2 contributes to suppression of a transcriptional program that is detrimental to adult neuron function and survival (22). Knockdown of Ezh1 in the adult mouse prefrontal cortex attenuates sociability and promotes motivational behaviors (28). Therefore, it is of interest to determine which targets can be regulated by Ezh1 in postmitotic neurons.…”