title: Histone modifications as a pathogenic mechanism of colorectal tumorigenesis.
abstract: Epigenetic regulation of gene expression has provided colorectal cancer (CRC) pathogenesis with an additional trait during the past decade. In particular, histone post-translational modifications set up a major component of this process dictating chromatin status and recruiting non-histone proteins in complexes formed to "handle DNA". In CRC, histone marks of aberrant acetylation and methylation levels on specific residues have been revealed, along with a plethora of deregulated enzymes that catalyze these reactions. Mutations, deletions or altered expression patterns transform the function of several histone-modifying proteins, further supporting the crucial role of epigenetic effectors in CRC oncogenesis, being closely associated to inactivation of tumor suppressor genes. Elucidation of the biochemical basis of these new tumorigenic mechanisms allows novel potential prognostic factors to come into play. Moreover, the detection of these changes even in early stages of the multistep CRC process, along with the reversible nature of these mechanisms and the technical capability to detect such alterations in cancer cells, places this group of covalent modifications as a further potential asset for clinical diagnosis or treatment of CRC. This review underlines the biochemistry of histone modifications and the potential regulatory role of histone-modifying proteins in CRC pathogenesis, to date. Furthermore, the underlying mechanisms of the emerging epigenetic interplay along with the chemical compounds that are candidates for clinical use are discussed, offering new insights for further investigation of key histone enzymes and new therapeutic targets.
authors.affiliation: Department of Biological Chemistry, University of Athens, Medical School, 11527 Athens, Greece. papavas@med.uoa.gr
authors.forename: Antonios N
authors.initials: AN
authors.lastname: Gargalionis
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.forename: Christos
authors.initials: C
authors.lastname: Adamopoulos
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
mesh_terms: D000107:Acetylation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008954:Models, Biological; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones