Assay of LGI1 gene epigenetic alterations by posttranslational modifications of H3 histone in malignant gliomas

Abstract

Although progress has been made 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 glioma malignant transformation is accompanied by gradual loss of LGI1 gene expression. However, genetic defects underlying LGI1 inactivation are not recognized. In this work, we analyzed LGI1 gene expression in primary cultures of malignant gliomas and compared these data with posttranslational modifications of H3 histone, an epigenetic indicator of transcriptional activity. We showed the presence of an epigenetic marker of gene repression H3K9me3 near LGL1 transcription initiation site in most malignant gliomas (five out of six). No expression of LGI1 gene was registered in these gliomas. LGI1 expression was documented only in one glioma, and this tumor did not exhibit an association of LGI1 gene with H3K9me3 modification. Thus, we demonstrated for the first time a correlation between an LGI1 gene expression and epigenetic indicator H3K9met3 in malignant gliomas. An Н3К4ас marker of actively transcribed chromatin near LGI1 transcription initiation site was not found. These data suggest the inactivation of LGI1 gene through an epigenetic mechanism: a modified “histone code.”