Epigenetics and reproduction and the developmental origins of health and disease

Ano: 2010 | Volume: 7 | Número: 3

Autores: K. Aagaard-tillery, M. Suter, A. Harris, A. Abramovici, J. Cantu

Palavras-chave: chromatin, developmental origins of disease, dna methylation, histone modification, nutrition, pregnancy, tobacco

Resumo Inglês:

Over the past century, studies of development and reproductive biology have transcended our understandings of what constitutes heritability and the acquisition of phenotypic traits from one generation to the next. While our early research defined “particulate genetic inheritance” as a primary mechanism for the heritability of traits, more recent work in past decades in lower eukaryotes and early mammalian species have included “epigenetic” (or “upon the genome”) modifications to the genomic backbone as a primary mechanism in the complex series of molecular interactions which ultimately enabling coordinate regulation of development. In recent years such investigations have evolved to focus on the role of epigenetic modifications to DNA and core histones in higher mammalian developmental processes. What are epigenetic modifications? While almost all cells of an individual bear near identical genomic constitutions, phenotype is ultimately determined by the gene expression profile. Gene expression is maintained by two major mechanisms: (1) transcription factors and post-transcriptional modifiers, and (2) epigenetic modifications, in particular DNA and core-histone modifications, that can be inherited during mitosis from one cell generation to another. This epigenetic code is essential in directing the tremendous number of gene expression changes that must occur for a cell to leave its pluripotent state and become fully differentiated to then function in adaptive homeostasis processes of the organism. It may therefore be stated that one’s epigenetic signatures are the net outcome of genotype, developmental lineage, and environmental exposures. These epigenetic signatures are stable and/or heritable patterns of gene activity and expression that do not result from changes in the genomic sequence. Covalent modifications to histones (i.e., histone H3 acetylation and methylation) and DNA methylation (meCpG) are examples of such epigenetic events which collectively act as a “memory” to maintain gene expression profiles after cell division. Research is rapidly demonstrating the importance of the epigenetic code to normal human development as well as the burden of disease that occurs when the epigenetic code or machinery malfunctions. In essence, epigenetic modulation results in functional adaptations of the genomic response to the environment and is believed to play a fundamental role in early developmental plasticity. This review provides and overview on studies related to reproduction and epigenetic inheritance, many of which have arisen from the Developmental Origins of Adult Health and Disease fields