Above and within the genome: epigenetics past and present.
Epigenetic regulation involves the maintenance of a particular state of gene expression--most commonly, repression--in the face of repeated mitosis, and frequently meiosis. Remarkably, changes in such heritable expression states occur without an alteration of the primary DNA sequence. We present a brief history of research in epigenetics, beginning with pioneering work in the 1950s by B. McClintock and R. A. Brink on maize kernel color inheritance. We describe the complex biochemistry of DNA methylation--the molecular basis of most epigenetic regulation in mammalian genomes--and review data connecting it to targeted modification and remodeling of chromatin structure. Several prominent examples of epigenetically regulated loci--X chromosome inactivation, imprinting, repetitive DNA silencing, and aberrant methylation patterns in neoplasia--are reviewed along with a description of our current understanding of the underlying molecular mechanisms. A common theme that emerges is the complex integration of epigenetic regulatory pathways with the chromatin infrastructure over target DNA loci.
Urnov
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FD
Sangamo Biosciences, Richmond, California 94804, USA. furnov@sangamo.com
Wolffe
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AP
D002843:Chromatin / Q000235:genetics*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D030342:Genetic Diseases, Inborn / Q000235:genetics; D016678:Genome; D006657:Histones / Q000737:chemistry*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D004248:DNA (Cytosine-5-)-Methyltransferases