Cancer and epigenesis: a developmental perspective.
Traditionally, molecular geneticists have studied the genome, that is, DNA. This has included its sequencing, with identification of promoters, enhancers, introns, exons, and mutations. During the last 10 to 15 years, it has become clear that this study of "naked" DNA imposed major limitations on our understanding of gene regulation, and that DNA must be studied in conjunction with its protein backbone (chromatin). This new vision has shown that chromatin is a very dynamic molecule, and that changes in DNA methylation, in histones leg, their localization, density, and whether they are acetylated, methylated, phosphorylated and/or ubiquitinated), and in the Polycomb-Trithorax equilibrium are all crucial for the control of gene expression. Furthermore, it was found that like DNA, chromatin-related proteins and DNA methylation are generally passed on unchanged from one cell to its daughters. Thus, gene expression is partly controlled through chromatin modifications that are transmitted from one cell to all its descendants. Such a control is referred to as "epigenetic," as the DNA sequence is not altered. Hence, these epigenetic "marks" can be erased in the early embryo, rendering these cells totipotent. This chapter presents a basic overview of epigenesis in the control of normal embryonal cell differentiation, including imprinting. Similarities between embryonal and cancer cells are highlighted, and the potential impact of chemotherapy aimed at epigenetic mechanisms is reviewed.
Oligny
Luc Laurier
LL
Department of Pathology and Cellular Biology, Faculty of Medicine, University of Montreal, and Hôpital Sainte-Justine, Montreal, Quebec, Canada.
D000483:Alleles; D002843:Chromatin / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D044127:Epigenesis, Genetic / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics; D042421:Histone Code / Q000235:genetics; D006801:Humans; D000074081:MutS Homolog 3 Protein; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D017354:Point Mutation / Q000235:genetics; D063146:Polycomb-Group Proteins; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012641:Selection, Genetic; D014157:Transcription Factors / Q000235:genetics
D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C420116:Ihit1 protein, mouse; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; D063146:Polycomb-Group Proteins; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C063460:Trl protein, Drosophila