MECHANISM OF GENOMIC IMPRINTING DURING SPERMATOGENESIS

描述（改编自研究者摘要）：基因组印记是 在配子形成过程中某些基因被标记的过程， 差异表达亲本等位基因。 那些支配着 在亲本的生殖系中建立等位基因特异性表达 在配子发生过程中，这样雄性亲本就赋予了父亲的印记 他的染色体在精子发生过程中，和女性的父母赋予一个 卵子发生过程中的母性印记 此应用程序将集中于 建立父系印记的分子基础 精子发生 Prader-Willi（PWS）和Angelman的分子分析 (AS)在人类15 q11 -13中发现了一种功能性印记 中心（IC），并提供了对可能调节 在配子发生过程中的印记。 国际社会的两个次区域 15 q11 -13中的印记基因簇控制初级父系， 多个基因的母体特异性印记。 IC的3 kb亚区 (the PWS IC），其包括印迹基因的外显子1和启动子区。 SNRPN基因在父系印记的形成中起主要作用 在精子发生过程中。 该亚区的突变通过以下方式导致PWS： 阻止在15 q11 -13基因上建立父系印记， 在精子发生过程中破坏整个区域的印记。 一旦 在PWS IC中设置了一个主要的父系特定印记，该主要印记 然后，印迹信号必须传递到每个印迹基因， 15 q11 -13，以建立基因表达的父系模式。 无论是 也不包括用于传送主IC印记的机构 目前已知对单个基因信号传导。 此应用程序将 确定主要和基因特异性的性质和时间 小鼠7 C染色体PWS/AS共振区的印迹信号 在精子发生过程中。 来自小鼠不同阶段的细胞 将分离精子发生并检查差异DNA 甲基化，DNase I超敏位点和DNA-蛋白质相互作用， 小鼠7 C，这可能是指示的主要和基因特异性印记 信号. 了解印迹的分子基础可能会导致 用于治疗已知涉及以下的遗传性疾病的治疗方法 印记

DESCRIPTION (Adapted from investigator's abstract): Genomic imprinting is the process by which certain genes are marked during gametogenesis to differentially express the parental alleles. The imprints that govern allele-specific expression are established in the germline of the parents during gametogenesis, such that the male parent confers a paternal imprint to his chromosomes during spermatogenesis, and the female parent confers a maternal imprint during oogenesis. This application will focus on the molecular basis for establishment of the paternal imprint during spermatogenesis. Molecular analysis of the Prader-Willi (PWS) and Angelman (AS) syndromes in human 15q11-13 has identified a functional imprinting center (IC) and provided insight into the mechanisms that may regulate imprinting during gametogenesis. Two subregions of the IC within the cluster of imprinted genes in 15q11-13 control the primary paternal- and maternal-specific imprinting of multiple genes. A 3 kb subregion of the IC (the PWS IC) that includes exon 1 and the promoter region of the imprinted SNRPN gene appears to play the primary role in setting the paternal imprint during spermatogenesis. Mutations in this subregion lead to PWS by preventing the establishment of a paternal imprint on genes in 15q11-13 and disrupting imprinting throughout this region in spermatogenesis. Once the primary paternal-specific imprint is set in the PWS IC, this primary imprinting signal must then be transmitted to each imprinted gene in 15q11-13 to establish the paternal pattern of gene expression. Neither the primary imprint nor the mechanism for transmitting the primary IC imprint signal to individual genes are currently known. This application will determine the nature and timing of both the primary and gene-specific imprinting signals in the PWS/AS syntonic region of mouse chromosome 7C during spermatogenesis. Cells from different stages of mouse spermatogenesis will be isolated and examined for differential DNA methylation, DNase I hypersensitive sites, and DNA-protein interactions in mouse 7C that may be indicative of the primary and gene-specific imprinting signals. Understanding the molecular basis of imprinting may lead to therapeutic approaches for treating genetic disorders known to involve imprinting.