Genetic Silencing in Germline Maintenance and Function

成体生殖细胞具有许多不同的功能，包括增殖、减数分裂突触和细胞分裂。 重组、母本和父本mRNA和蛋白质合成以及配子发生。它也有多个 义务，包括防止移动的遗传因素（转座子）对遗传的 损伤，阻止生殖细胞分化成体细胞，并建立遗传状态， 转录活性所有这些义务在某种程度上都是通过镇压机制来履行的， 制止或防止违反这些义务的不适当活动。生殖细胞阻遏 利用转录后抑制（例如，基于RNAi的）和转录的（例如， 基于染色质的）机制来实现其目标。这些机制的一个主要目标是X 染色体，这是转录抑制减数分裂过程中在两个性别的C。优雅，但完全是 在蠕虫和哺乳动物的雄性减数分裂期间失活。性染色体失活是由 一个高度保守的过程，在减数分裂过程中靶向未突触的染色质，很可能是一个古老的 基因组防御机制我们了解该机制的一些组成部分，并计划 利用C. elegans作为一个模型系统。在哺乳动物和 蠕虫，男性X是“印记”优先失活的胚胎，这可能是一个后果， 减数分裂沉默印记X染色体失活是遗传印记的一个引人注目的例子， 了解印记的建立。我们还将使用遗传、分子、生物化学和 可用的细胞学工具C. elegans来剖析雄性X印记的机制。我们已经使用了 广泛的工具可用于这种生物体，将其构建为研究生殖系的优秀模式生物 抑制，或沉默，现在准备解剖的作用，染色质在生殖细胞沉默， 建立和基因组防御机制。 在生殖系中运作的表观遗传机制对于建立印记和基因组是必不可少的。 预防可遗传的基因突变，这两者对正常的人类健康和正常的 人类发展

The adult germ line has many disparate functions, including proliferation, meiotic synapsis and recombination, maternal and paternal mRNA and protein synthesis, and gametogenesis. It also has multiple obligations, including preventing mobile genetic elements (transposons) from inflicting heritable genetic damage, preventing differentiation of the germ cells into somatic cells, and establishing heritable states of transcriptional activity. All of these obligations are met, to some extent, by repressive mechanisms that act to silence or prevent inappropriate activities that are counter to these obligations. Germ cell repression utilizes a combination of post-transcriptional repression (e.g., RNAi-based) and transcriptional (e.g., chromatin based) mechanisms to achieve its goals. A major target of these mechanisms is the X chromosome, which is transcriptionally repressed during meiosis in both sexes in C. elegans, but is fully inactivated during male meiosis in both worms and mammals. Sex chromosome inactivation is mediated by a highly conserved process that targets unsynapsed chromatin during meiosis, and is likely an ancient genome defense mechanism. We understand some of the components of the mechanism, and plan to further dissect the mechanism and its regulation using C. elegans as a model system. In both mammals and worms, the male X is "imprinted" for preferentially inactivation in embryos, and this is likely a consequence of its meiotic silencing. Imprinted X inactivation is a dramatic example of genetic imprinting, and little is understood about imprint establishment. We will also use the genetic, molecular, biochemical, and cytological tools available in C. elegans to dissect the mechanism of male X imprinting. We have used the extensive tools available for this organism to build it into an excellent model organism for studying germ line repression, or silencing, and are now poised to dissect the role of chromatin in germ cell silencing, imprint establishment and genome defense mechanisms in this genetic model system. Epigenetic mechanisms operating in the germ line are essential for the establishment of imprinting and the prevention of heritable genetic mutations, both of which are crucial for normal human health and normal human development.