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.
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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
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Supported by a grant from the Polish National Science Centre [DEC-2015/16/W/NZ2/00314].
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Ciechomska, I.A., Jayaprakash, C., Maleszewska, M., Kaminska, B. (2020). Histone Modifying Enzymes and Chromatin Modifiers in Glioma Pathobiology and Therapy Responses. In: Barańska, J. (eds) Glioma Signaling. Advances in Experimental Medicine and Biology, vol 1202. Springer, Cham. https://doi.org/10.1007/978-3-030-30651-9_13
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