title: Regulation of chromatin structure via histone post-translational modification and the link to carcinogenesis.
abstract: The loss of genome integrity contributes to the development of tumors. Although genome instability is associated with virtually all tumor types including both solid and liquid tumors, the aberrant molecular origins that drive this instability are poorly understood. It is now becoming clear that epigenetics and specific histone post-translational modifications (PTMs) have essential roles in maintaining genome stability under normal conditions. A strong relationship exists between aberrant histone PTMs, genome instability, and tumorigenesis. Changes in the genomic location of specific histone PTMs or alterations in the steady-state levels of the PTM are the consequence of imbalances in the enzymes and their activities catalyzing the addition of PTMs ("writers") or removal of PTMs ("erasers"). This review focuses on the misregulation of three specific types of histone PTMs: histone H3 phosphorylation at serines 10 and 28, H4 mono-methylation at lysine 20, and H2B ubiquitination at lysine 120. We discuss the normal regulation of these PTMs by the respective "writers" and "erasers" and the impact of their misregulation on genome stability.
authors.affiliation: Department of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Thompson
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Guppy
authors.forename: Laryssa
authors.initials: L
authors.lastname: Sawchuk
authors.forename: James R
authors.initials: JR
authors.lastname: Davie
authors.forename: Kirk J
authors.initials: KJ
authors.lastname: McManus
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004260:DNA Repair; D015972:Gene Expression Regulation, Neoplastic; D017781:Genes, Immediate-Early; D042822:Genomic Instability; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007399:Interphase; D008745:Methylation; D008938:Mitosis; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D059467:Transcriptome; D054875:Ubiquitination
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D056466:Histone Demethylases