THE ANALYSIS OF LGI1 GENE EPIGENETIC ALTERATIONS BY MEANS OF POSTTRANSLATIONAL H3 HISTONE MODIFICATIONS IN MALIGNANT...

Although there is a progress in understanding the causes and consequences of genetic and epigenetic changes in glioma malignant transformation, many details remain obscure and need further investigation. It is known that process of malignant transformation of gliomas is accompanied by gradual loss of LGI1 gene expression. However, genetic defects causing LGI1 inactivation have not been revealed. In this paper, we have analyzed the LGI1 gene expression in primary cultures of malignant gliomas, and compared these data with epigenetic indicators of transcriptional activity — posttranslational H3 histone modifications. We have show the presence of an epigenetic marker of gene repression H3K9me3 near the site of LGI1 transcription initiation in most (5 from 6) studied gliomas. There was not LGI1 expression in these gliomas. Only one glioma showed LGI1 expression, and in this glioma there was no association of LGI1gene with H3K9me3 modification. Thus, we are the first to show a correlation between LGI1 gene expression and the epigenetic indicator H3K9met3 in malignant gliomas. Marker of actively transcribed chromatin Í3K4àñ have not been found in this area of the genome. The data obtained strongly suggest the possibility of gene LGL1 inactivation by epigenetic mechanism: modified «histone code».