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  • The miR-124-Sox9 paramutation: RNA-mediated epigenetic control of embryonic and adult growth.

The miR-124-Sox9 paramutation: RNA-mediated epigenetic control of embryonic and adult growth.

Development (Cambridge, England) (2009-10-13)
Valérie Grandjean, Pierre Gounon, Nicole Wagner, Luc Martin, Kay D Wagner, Florence Bernex, François Cuzin, Minoo Rassoulzadegan
摘要

The size of the mammalian body is determined by genetic and environmental factors differentially modulating pre- and postnatal growth. We now report a control of growth acting in the mouse from the first cleavages to the postnatal stages. It was evidenced by a hereditary epigenetic modification (paramutation) created by injection of a miR-124 microRNA into fertilized eggs. From the blastocyst to the adult, mouse pups born after microinjection of this miRNA showed a 30% increase in size. At the blastocyst stage, frequent duplication of the inner cell mass resulted in twin pregnancies. A role of sperm RNA as a transgenerational signal was confirmed by the giant phenotype of the progeny of transgenic males expressing miR-124 during spermiogenesis. In E2.5 to E8.5 embryos, increased levels of several transcripts with sequence homology to the microRNA were noted, including those of Sox9, a gene known for its crucial role in the progenitors of several adult tissues. A role in embryonic growth was confirmed by the large size of embryos expressing a Sox9 DNA transgene. Increased expression in the paramutants was not related to a change in miR-124 expression, but to the establishment of a distinct, heritable chromatin structure in the promoter region of Sox9. While the heritability of body size is not readily accounted for by Mendelian genetics, our results suggest the alternate model of RNA-mediated heritable epigenetic modifications.

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Sigma-Aldrich
抗Sox9抗体, Chemicon®, from rabbit
Sigma-Aldrich
ChIPAb+三甲基组蛋白H3(Lys9) - ChIP免疫沉淀验证抗体和引物试剂套装, from rabbit
Sigma-Aldrich
ChIPAb+ 二甲基组蛋白H3(Lys9)- ChIP经验证的抗体和引物组, serum, from rabbit