Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas

绘制染色质可及性和活性调节元件揭示人类神经胶质瘤的病理机制

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作者:Karolina Stępniak #, Magdalena A Machnicka #, Jakub Mieczkowski #, Anna Macioszek, Bartosz Wojtaś, Bartłomiej Gielniewski, Katarzyna Poleszak, Malgorzata Perycz, Sylwia K Król, Rafał Guzik, Michał J Dąbrowski, Michał Dramiński, Marta Jardanowska, Ilona Grabowicz, Agata Dziedzic, Hanna Kranas, Karoli

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.

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