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MicroRNAs and cystic fibrosis--an epigenetic perspective 总被引:1,自引:0,他引:1
CF (cystic fibrosis) is a recessive genetic disease caused by mutations of the CFTR (cystic fibrosis transmembrane conductance regulator), a cAMP-activated anion channel, exhibiting a multitude of clinical manifestations including lung inflammation/infection, pancreatic insufficiency/diabetes, intestinal obstruction and infertility in both sexes. While mutation DF508 is found in 70% of CF patients, large variation in disease phenotypes and severity is observed among the patients. This review discusses current theories accounting for the disease variations and puts forth an epigenetic hypothesis involving microRNAs. 相似文献
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Shields ED 《American journal of physical anthropology》2005,128(2):299-311
This investigation of modern human mandibular premolar root variation tests the hypothesis that population-specific mandibular single-rooted premolar root size can predict a predisposition to root morphological complexity. Mandibular postcanines were examined and quantified from dental radiographs in a globally spread sample of 1,615 modern humans. Multirooted premolars and a fused molar root phenotype were investigated as probes into greater than, and less than, the normative root number. Twelve questions were addressed concerning root structure of mandibular premolars and second molars. A direct correlation was found between single-rooted mandibular premolar size and the predisposition to multirootedness. This correlation infers the following: 1) that postcanine primordia size during root formation predisposes to the development of more, or less, than the normative postcanine root number; and 2) that the epigenetic effect of tooth primordium size per se influences the induction of interradicular processes, which divides the root during its development. This simple developmental model helps explain the following observations: 1) population-specific variation in postcanine root number; 2) sexual dimorphism for multirooted mandibular premolar prevalence; 3) why microdont teeth are single-rooted; 4) the hierarchy of developmental canalization of interradicular processes; 5) megadont-hominin to late-hominin mandibular premolar root number transition; and 6) the fluctuation of mandibular premolar root number in primate evolutionary history. 相似文献
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In the past two years, a variety of forward genetic screens have revealed predicted plant chromatin remodeling components that are involved in either differential histone acetylation or ATP-dependent SWI2/SNF2-related complexes. Combined with the results of recent reverse genetic studies, these findings have begun to provide the groundwork for determining the function of chromatin-based control in plants. 相似文献
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The Complex Regulation of Senescence 总被引:1,自引:0,他引:1
Andreas M. Fischer 《植物科学评论》2012,31(2):124-147
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Paul L. Severson Erik J. Tokar Lukas Vrba Michael P. Waalkes Bernard W. Futscher 《Epigenetics》2012,7(11):1238-1248
Epigenetic dysfunction is a known contributor in carcinogenesis, and is emerging as a mechanism involved in toxicant-induced malignant transformation for environmental carcinogens such as arsenicals or cadmium. In addition to aberrant DNA methylation of single genes, another manifestation of epigenetic dysfunction in cancer is agglomerative DNA methylation, which can participate in long-range epigenetic silencing that targets many neighboring genes and has been shown to occur in several types of clinical cancers. Using in vitro model systems of toxicant-induced malignant transformation, we found hundreds of aberrant DNA methylation events that emerge during malignant transformation, some of which occur in an agglomerative fashion. In an arsenite-transformed prostate epithelial cell line, the protocadherin (PCDH), HOXC and HOXD gene family clusters are targeted for agglomerative DNA methylation. The agglomerative DNA methylation changes induced by arsenicals appear to be common and clinically relevant events, since they occur in other human cancer cell lines and models of malignant transformation, as well as clinical cancer specimens. Aberrant DNA methylation in general occurred more often within histone H3 lysine-27 trimethylation stem cell domains. We found a striking association between enrichment of histone H3 lysine-9 trimethylation stem cell domains and toxicant-induced agglomerative DNA methylation, suggesting these epigenetic modifications may become aberrantly linked during malignant transformation. In summary, we found an association between toxicant-induced malignant transformation and agglomerative DNA methylation, which lends further support to the hypothesis that epigenetic dysfunction plays an important role in toxicant-induced malignant transformation. 相似文献