Anti-SYN2 monoclonal antibody, clone FQS4387

a-Kleisins are core components of meiotic and mitotic cohesin complexes. Arabidopsis contains four genes that encode a-kleisin proteins: SYN1, SYN2, SYN3 and SYN4. SYN1, a REC8 ortholog, is essential for meiosis, while SYN2 and SYN4 appear to be SCC1 orthologs and function in mitosis. SYN3 is essential for megagametogenesis and is enriched in the nucleolus of meiotic and mitotic cells. In this study the role of SYN3 during meiosis was investigated by characterization of plants that express SYN3-RNAi constructs from either meiotic DMC1, native SYN3, or inducible PX7 promoters. Reduction of SYN3 caused defects in homologous chromosome synapsis and synaptonemal complex (SC) formation during male and female meiosis. Consistent with this observation, relatively little signal for the SC component ZYP1 was detected on the chromosomes of SYN3-RNAi plants. ZYP1 transcript levels were relatively normal, but several transcripts for genes that encode proteins involved in meiotic recombination were altered, which suggested that a reduction in SYN3 may inhibit meiotic progression by alteration of meiotic gene expression.

The synapsin family of neuronal phosphoproteins is composed of three genes (SYN1, SYN2 and SYN3) with alternative splicing resulting in a number of variants with various levels of homology. These genes have been postulated to play significant roles in several neuropsychiatric disorders, including bipolar disorder, schizophrenia and epilepsy. Epigenetic regulatory mechanisms, such as histone modifications in gene regulatory regions, have also been proposed to play a role in a number of psychiatric disorders, including bipolar disorder and major depressive disorder. One of the best characterized histone modifications is histone 3 lysine 4 tri-methylation (H3K4me3), an epigenetic mark shown to be highly enriched at transcriptional start sites and associated with active transcription. In the present study we have quantified the expression of transcript variants of the three synapsin genes and investigated their relationship to H3K4me3 promoter enrichment in post-mortem brain samples. We found that histone modification marks were significantly increased in bipolar disorder and major depression and this effect was correlated with significant increases in gene expression. Our findings suggest that synapsin dysregulation in mood disorders is mediated in part by epigenetic regulatory mechanisms.