12/20/2007

epigenetics

Genetic expression has traditionally been understood as one-gene-one-protein, however, much genetic expression is regulated through reversible and transmissable epigenetic mechanisms, which act without an alteration of archival DNA.

Epigenetics includes the phenomenon within molecular genetics whereby a single sequence of DNA can give rise, through alternative splicing, to multiple versions of mRNA, and hence to multiple proteins, thus increasing complexity and fine-tuning genetic expression. Epigenetics also refers to DNA related mechanisms of inheritance, such as methylation and chromatin assembly.

Epigenetic regulation of gene expression is mediated through alterations in DNA methylation, covalent modifications of core nucleosomal histones, rearrangement of histones, transposon function, chromosome imprinting, type switching, telomeric silencing, and by RNA interference. Genomic imprinting is a form of mammalian epigenetic regulation which results in the silencing of one copy (allele) of specific genes, according to parental origin. Recently, protein complexes have been discovered to manipulate nucleosomes, organize larger chromatin domains, and set boundaries of chromatin structure. Thus, key histone modifications, cis-acting elements, and regulatory proteins set, maintain, and reprogram epigenetic memory.

Epigenetic mechanisms also operate as conditional, non-programmed interactions that determine individual development [s]:
1. Interactions of cell metabolism with the external and internal physicochemical environment of an organism.
2. Interactions of tissue masses with the physical environment on the basis of physical laws inherent to condensed materials.
3. Interactions among tissues themselves.

Deregulation of epigenetic mechanisms cooperates with genetic alterations in the development and progression of malignancies. Loss of epigenetic regulation is also implicated in systemic disease. Epigenetic deregulation affects several aspects of the biology of tumor cells, including cell cycle control, differentiation, cell growth, DNA repair, and cell death.

In plants, epigenetic alterations that occur during somatic growth can be transmitted to the progeny because germ cells differentiate from somatic tissues only after many cycles of mitotic divisions.

See alternative splicing

Defining epigenetic states through chromatin and RNA - Nature Genetics: "The term 'epigenetics' is used to describe heritable changes in genome function that occur without a change in DNA sequence. As such, epigenetics lies at the heart of the cellular memory crucial for development and provides an important avenue for sustained response to environmental stimuli."

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External : Transposons part 1, transposons part 2 : Barbara McClintock and mobile genetic elements :

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