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

Nat Commun. 2021 Jun 15;12(1):3621. doi: 10.1038/s41467-021-23922-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Brain Neoplasms / genetics
  • Chromatin Immunoprecipitation
  • Chromatin*
  • 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

Substances

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