Deregulation of histone-modifying enzymes and chromatin structure modifiers contributes to glioma development.
The epigenetic landscape is deregulated in cancer due to aberrant activation or inactivation of enzymes maintaining and modifying the epigenome. Histone modifications and global aberrations at the histone level may result in distorted patterns of gene expression, and malfunction of proteins that regulate chromatin modification and remodeling. Recent whole genome studies demonstrated that histones and chaperone proteins harbor mutations that may result in gross alterations of the epigenome leading to genome instability. Glioma development is a multistep process, involving genetic and epigenetic alterations. This review summarizes newly identified mechanisms affecting expression/functions of histone-modifying enzymes and chromatin modifiers in gliomas. We discuss recent approaches to overcome epigenetic alterations with histone-modifying enzyme inhibitors and their prospects for glioma therapy.
Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology, 3 Pasteur Str., 02-093 Warsaw, Poland.
Marta
M
Maleszewska
Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology, 3 Pasteur Str., 02-093 Warsaw, Poland.
Bozena
B
Kaminska
D000367:Age Factors; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009707:Nucleosomes / Q000378:metabolism
D000970:Antineoplastic Agents; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009707:Nucleosomes
epi-drugs; gliomas; histone modifications; histone-modifying enzyme inhibitors; transcription regulation