Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas
Karolina Stępniak, Magdalena A. Machnicka, Jakub Mieczkowski, Anna Macioszek, Bartosz Wojtaś, Bartłomiej Gielniewski, Katarzyna Poleszak, Małgorzata Perycz, Sylwia Król, Rafał Guzik, Michał J. Dąbrowski, Michał Dramiński, Marta Jardanowska, Ilona E. Grabowicz, Agata Dziedzic, Hanna Kranas, Karolina Sienkiewicz, Klev Diamanti, Katarzyna Kotulska, Wiesława Grajkowska, Marcin Roszkowski, Tomasz Czernicki, Andrzej Marchel, Jan Komorowski, Bożena Kamińska, Bartek Wilczyński
Abstract
Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.