Replication of heterochromatin: insights into mechanisms of epigenetic inheritance.
ABSTRACT Heterochromatin is composed of tightly condensed chromatin in which the histones are deacetylated and methylated, and specific nonhistone proteins are bound. Additionally, in vertebrates and plants, the DNA within heterochromatin is methylated. As the heterochromatic state is stably inherited, replication of heterochromatin requires not only duplication of the DNA but also a reinstallment of the appropriate protein and DNA modifications. Thus replication of heterochromatin provides a framework for understanding mechanisms of epigenetic inheritance. In recent studies, roles have been identified for replication factors in reinstating heterochromatin, particularly functions for origin recognition complex, proliferating cell nuclear antigen, and chromatin-assembly factor 1 in recruiting the heterochromatin binding protein HP1, a histone methyltransferase, a DNA methyltransferase, and a chromatin remodeling complex. Potential mechanistic links between these factors are discussed. In some cells, replication of the heterochromatin is blocked, and in Drosophila this inhibition is mediated by a chromatin binding protein SuUR.
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ABSTRACT: Finalist (teleological) implications have been described for both Darwinian and Lamarckian theories, even though finalism appears to be more commonly associated with Lamarckism. Biologists have focused on finding final causes to explain evolutionary novelties through, for example, applying the “what for?” question to address experimental observations. Now epigenetics, together with developmental biology, may allow us to focus on the efficient causes leading to evolutionary change, asking the “how?” question, considering environmental influences as inducers of genomic change. This is a whole under-studied dimension in evolutionary studies. In this paper, I discuss how epigenetics and developmental biology can help integrate two important ways in which the environment affects evolution: through inducing or through restricting the emergence of new phenotypes. I also discuss which aspects of both theories should be reconsidered in the face of current knowledge in epigenetics and where the emphasis of evolutionary experiments should be placed. Important goals of evolution related epigenetic studies should be: (i) to experimentally consider the separation among the origin of characters in a lineage and its further fixation, in order to address these processes in a proper dimension, (ii) to build the cause-effect relation between the factors inducing epigenetic changes and consequent changes in population parameters, and (iii) to consider that the arising of new characters is modulated by physiological and developmental constraints, and that this process is not related to a purpose or focused to solve an ecological, physiological or evolutionary challenge.Evolutionary Biology 03/2012; 39(3):283-300. · 2.39 Impact Factor
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ABSTRACT: The remarkable ability of many parasites to evade host immunity is the key to their success and pervasiveness. The immune evasion is directly linked to the silencing of the members of extended families of genes that encode for major parasite antigens. At any time only one of these genes is active. Infrequent switches to other members of the gene family help the parasites elude the immune system and cause prolonged maladies. For most pathogens, the detailed mechanisms of gene silencing and switching are poorly understood. On the other hand, studies in the budding yeast Saccharomyces cerevisiae have revealed similar mechanisms of gene repression and switching and have provided significant insights into the molecular basis of these phenomena. This information is becoming increasingly relevant to the genetics of the parasites. Here we summarize recent advances in parasite epigenetics and emphasize the similarities between S. cerevisiae and pathogens such as Plasmodium, Trypanosoma, Candida, and Pneumocystis. We also outline current challenges in the control and the treatment of the diseases caused by these parasites and link them to epigenetics and the wealth of knowledge acquired from budding yeast.Epigenetics & Chromatin 11/2013; 6(1):40. · 4.19 Impact Factor
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ABSTRACT: Nonylphenol (NP) is an environmental endocrine-disrupting chemical that has been detected in human cord blood and milk. Developmental exposure to NP is unavoidable and can lead to hyperadrenalism, a syndrome that resembles Cushing's disease and has a life-long impact on the affected individual. In this study, we investigated the recovery of female rats from developmental exposure to NP and the effects of such exposure on future generations. Female rats were time-mated, and rats in the experimental group (NP group) were administered NP in drinking water (2μg/mL) throughout gestation and lactation. Pregnant females in the control group were given water only (Veh group). The resulting litters were recognized as the first-generation F1 offspring. The F1 females were time-mated with non-sibling F1 males within the same treatment group. NP was not administered after the F0 generation. The treatment procedures for F3 offspring were identical to those for the F2 generation. The experimental results showed that the observed characteristics of the F3 NP generation had reverted to normal and resembled those of the F3 Veh generation. Thus, our study indicated that developmental exposure to NP resulted in a life-long impact on the exposed individual, but that recovery to the "normal" state was possible if further NP exposure was prevented.Chemico-Biological Interactions 08/2014; · 2.97 Impact Factor