Comprehensive analysis of the transcription factor REST regulatory networks in IDH-mutant and IDH-wild type glioma

Abstract

SummaryREST acts as a transcriptional repressor of neuronal genes in non-neuronal cells but could be a transcriptional activator under certain conditions. REST was implicated in a blockage of cell differentiation and is an important oncogenic factor. As IDH mutations are oncogenic drivers in gliomas causing significant changes in the epigenome and blocking differentiation, we aimed at defining the role of REST in the IDH mutation-related phenotype in gliomas. We studied consequences of REST knockdown in IDH wild-type and mutant U87 cells. Chromatin immunoprecipitation followed by sequencing combined with transcription factor (TF) motif identification and transcriptome analyses revealed different patterns of REST binding and its proximal TF motifs in IDH wild-type and mutant U87 cells. Moreover, we identified putative targets of REST as related to ECM organization and cell differentiation. We demonstrate that the REST role in gliomas is dependent on IDH mutation status.Graphical abstract