Oncohistones: a roadmap to stalled development.
Antineoplastic Agents
/ therapeutic use
Carcinogenesis
/ genetics
Cell Differentiation
Chromatin
/ chemistry
Complementary Therapies
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Histones
/ genetics
Humans
Methylation
/ drug effects
Molecular Targeted Therapy
Mutation
Neoplasms
/ drug therapy
Neoplastic Stem Cells
/ drug effects
Oncogenes
Polycomb-Group Proteins
/ genetics
Protein Processing, Post-Translational
H3
development
differentiation
epigenome
oncohistones
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
17
04
2021
received:
17
02
2021
accepted:
07
05
2021
pubmed:
11
5
2021
medline:
9
3
2022
entrez:
10
5
2021
Statut:
ppublish
Résumé
Since the discovery of recurrent mutations in histone H3 variants in paediatric brain tumours, so-called 'oncohistones' have been identified in various cancers. While their mechanism of action remains under active investigation, several studies have shed light on how they promote genome-wide epigenetic perturbations. These findings converge on altered post-translational modifications on two key lysine (K) residues of the H3 tail, K27 and K36, which regulate several cellular processes, including those linked to cell differentiation during development. We will review how these oncohistones affect the methylation of cognate residues, but also disrupt the distribution of opposing chromatin marks, creating genome-wide epigenetic changes which participate in the oncogenic process. Ultimately, tumorigenesis is promoted through the maintenance of a progenitor state at the expense of differentiation in defined cellular and developmental contexts. As these epigenetic disruptions are reversible, improved understanding of oncohistone pathogenicity can result in needed alternative therapies.
Identifiants
pubmed: 33969633
doi: 10.1111/febs.15963
pmc: PMC9990449
mid: NIHMS1872913
doi:
Substances chimiques
Antineoplastic Agents
0
Chromatin
0
Histones
0
Polycomb-Group Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1315-1328Subventions
Organisme : NCI NIH HHS
ID : P01 CA196539
Pays : United States
Organisme : CIHR
ID : MOP-286756
Pays : Canada
Organisme : CIHR
ID : FDN-154307
Pays : Canada
Informations de copyright
© 2021 Federation of European Biochemical Societies.
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