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Histone Modifying Enzymes and Chromatin Modifiers in Glioma Pathobiology and Therapy Responses

  • Iwona A. Ciechomska
  • Chinchu Jayaprakash
  • Marta Maleszewska
  • Bozena KaminskaEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1202)

Abstract

Signal transduction pathways directly communicate and transform chromatin to change the epigenetic landscape and regulate gene expression. Chromatin acts as a dynamic platform of signal integration and storage. Histone modifications and alteration of chromatin structure play the main role in chromatin-based gene expression regulation. Alterations in genes coding for histone modifying enzymes and chromatin modifiers result in malfunction of proteins that regulate chromatin modification and remodeling. Such dysregulations culminate in profound changes in chromatin structure and distorted patterns of gene expression. Gliomagenesis is a multistep process, involving both genetic and epigenetic alterations. Recent applications of next generation sequencing have revealed that many chromatin regulation-related genes, including ATRX, ARID1A, SMARCA4, SMARCA2, SMARCC2, BAF155 and hSNF5 are mutated in gliomas. In this review we summarize newly identified mechanisms affecting expression or functions of selected histone modifying enzymes and chromatin modifiers in gliomas. We focus on selected examples of pathogenic mechanisms involving ATRX, histone methyltransferase G9a, histone acetylases/deacetylases and chromatin remodeling complexes SMARCA2/4. We discuss the impact of selected epigenetics alterations on glioma pathobiology, signaling and therapeutic responses. We assess the attempts of targeting defective pathways with new inhibitors.

Keywords

Histone modifications Transcription regulation Glioma, histone modifying enzyme inhibitors Epi-drugs 

Abbreviations

ADAADiN

Active DNA-dependent ATPase A domain inhibitor

ARID1A

AT-rich interactive domain-containing protein 1A

ATG

Autophagy related gene

ATRX

Thalassaemia/mental retardation syndrome X-linked

BET

Bromodomain and extraterminal domain

BRD

Bromodomain

DAXX

Death-domain associated protein

DNMT1

DNA methyltransferase-1

DSB

Double-strand break

EHMT2

Euchromatic histone-lysine N-methyltransferase 2

EZH2

Enhancer of zeste homolog 2

GBM

Glioblastoma

GLP

G9a-like protein

GSC

Glioma stem cell

HAT

Histone acetyltransferase

HDAC

Histone deacetylase

HMT

Histone methyltransferase

MBT domain

Malignant brain tumor domain

pCAF

p300/CBP Associated factor

PcG protein

Polycomb Group protein

RPA70

Replication protein A 70

SAM

S-adenosyl-methionine

SMARCA2

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 2

SMARCA4

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4

Suv39h1

Suppressor of variegation 3–9 homologue 1

SWI/SNF

SWItch/sucrose non-fermentable

TCGA

The cancer genome atlas

TMZ

Temozolomide

Notes

Acknowledgements

Supported by a grant from the Polish National Science Centre [DEC-2015/16/W/NZ2/00314].

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Iwona A. Ciechomska
    • 1
  • Chinchu Jayaprakash
    • 1
  • Marta Maleszewska
    • 1
  • Bozena Kaminska
    • 1
    Email author
  1. 1.Laboratory of Molecular Neurobiology, Neurobiology CenterNencki Institute of Experimental BiologyWarsawPoland

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