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

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.

• Authors: 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, Karolina Sienkiewicz, Klev Diamanti, Katarzyna Kotulska, Wiesława Grajkowska, Marcin Roszkowski, Tomasz Czernicki, Andrzej Marchel, Jan Komorowski, Bozena Kaminska, Bartek Wilczyński
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 3621 (06 15 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 34131149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromatin
• DNA-Binding Proteins
• FOXM1 protein, human
• Forkhead Box Protein M1
• Histones
• Transcription Factors
• DNA
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein

Topics

• Binding Sites
• Brain Neoplasms (genetics)
• Chromatin
• Chromatin Immunoprecipitation
• DNA (metabolism)
• DNA Methylation
• DNA-Binding Proteins (metabolism)
• Enhancer of Zeste Homolog 2 Protein
• Epigenesis, Genetic
• Epigenomics
• Forkhead Box Protein M1
• Gene Expression
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Glioblastoma
• Glioma (genetics)
• Histone Code
• Histones
• Humans
• Promoter Regions, Genetic
• Regulatory Sequences, Nucleic Acid
• Transcription Factors (metabolism)