Competitive signal discrimination, methylation reprogramming and genomic imprinting.
Genomic imprinting (parent-of-origin-dependent gene regulation) is associated with intra-genomic evolutionary conflict over the optimal pattern of gene expression. Most theoretical models of imprinting focus on the conflict between the maternally and paternally derived alleles at an imprinted locus. Recently, however, more attention has been focused on multi-directional conflicts involving not only the imprinted gene itself, but also the genes that encode the regulatory machinery responsible for establishing and maintaining imprinted gene expression. In this paper, I examine the conflict involved in epigenetic reprogramming of imprinted genes in early mammalian embryonic development. In the earliest phase of development, maternal-store proteins are responsible for most regulatory activity in the embryo. These proteins are under selection to maximize the mother's inclusive fitness, which is not identical to that of either of the sets of genes present in the embryo. Both the maternally and paternally derived genomes in the embryo favor maintenance of the epigenetic modifications established in the female and male germlines, respectively. Maternal-store proteins favor maintenance of some of these modifications, but erasure of others. Here I consider the logical structure of the machinery responsible for these two activities. Methylation maintenance is most effectively performed by AND-linked architectures, which may explain the unusual trafficking behavior of the oocyte-specific DNA methyltransferase, Dnmt1o. By contrast, demethylation is better supported by OR-linked architectures, which may explain the difficulty in identifying the factor(s) responsible for the active demethylation of the paternal genome following fertilization.
Wilkins
Jon F
JF
Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA. wilkins@santafe.edu
D000483:Alleles; D000818:Animals; D003198:Computer Simulation; D019175:DNA Methylation; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008322:Mammals / Q000196:embryology*; D008957:Models, Genetic; D011247:Pregnancy