mutants in the mouse nurdmi2 component p66α are embryonic lethal突变体在鼠标nurdmi2组件p66α胚胎致死.pdfVIP

Mutants in the Mouse NuRD/Mi2 Component P66a Are Embryonic Lethal Susan Marino, Roel Nusse* Howard Hughes Medical Institute, Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, California, United States of America Background. The NuRD/Mi2 chromatin complex is involved in histone modifications and contains a large number of subunits, including the p66 protein. There are two mouse and human p66 paralogs, p66a and p66b . The functions of these genes are not clear, in part because there are no mutants available, except in invertebrate model systems. Methodology. We made loss of function mutants in the mouse p66a gene (mp66a, official name Gatad2a, MGI:2384585). We found that mp66a is essential for development, as mutant embryos die around day 10 of embryogenesis. The gene is not required for normal blastocyst development or for implantation. The phenotype of mutant embryos and the pattern of gene expression in mutants are consistent with a role of mp66a in gene silencing. Conclusion. mp66a is an essential gene, required for early mouse development. The lethal phenotype supports a role in execution of methylated DNA silencing. Citation: Marino S, Nusse R (2007) Mutants in the Mouse NuRD/Mi2 Component P66a Are Embryonic Lethal. PLoS ONE 2(6): e519. doi:10.1371/ journal.pone.0000519 INTRODUCTION the NuRD/Mi2 complex (Figure 1) and acts in the nucleus where Epigenetic changes in gene expression, such as occurring during it is localized to both euchromatic and heterochromatic foci, imprinting and X chromosome inactivation, can result from DNA suggesting a role in facultative gene activity [10]. MeCP2 interacts methylation and from chromatin remodeling. The latter incl