title: Genetic lesions and perturbation of chromatin architecture: a road to cell transformation.
abstract: Differential gene expression is a rigorously precise procedure that defines the developmental program of cells, tissues, organs, and of the entire organism. The correct execution of this program requires the participation of multiple and complex groups of regulators. In addition to transcription factors, which are key tools in ontogenesis by providing sequential switch of different genes, the structure of the chromatin is a dominant determinant leading to gene expression. Through the novel and insightful work of several investigators, it appears that the architecture of the chromatin spanning the genes can and does influence the efficiency of RNA transcription, and therefore of gene expression. Several new enzymatic complexes have been identified that reversibly modify the chromatin architecture by methylation, phosphorylation, and acetylation of the nucleosomal core proteins. These enzymes are crucial for the proper balance and maintenance of gene expression, and are often the target of mutations and alterations in human cancer. Here, we review briefly the current models proposing how some of these enzymes normally modify the chromatin structure and how their functional disruption leads to inappropriate gene expression and cell transformation.
authors.affiliation: Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chakraborty
authors.forename: V
authors.initials: V
authors.lastname: Senyuk
authors.forename: G
authors.initials: G
authors.lastname: Nucifora
mesh_terms: D000107:Acetylation; D020816:Amino Acid Motifs; D000818:Animals; D050882:CREB-Binding Protein; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure*; D002869:Chromosome Aberrations; D019281:Dimerization; D005786:Gene Expression Regulation / Q000502:physiology; D018390:Gene Targeting; D006657:Histones / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D008745:Methylation; D051379:Mice; D008957:Models, Genetic; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D051958:Nuclear Receptor Coactivator 2; D009707:Nucleosomes / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D009707:Nucleosomes; D015514:Oncogene Proteins, Fusion; D018168:Receptors, Retinoic Acid; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse