Identification of regulatory elements responsible for genomic imprinting in mammals

鉴定负责哺乳动物基因组印记的调控元件

• 批准号: 5370906
• 负责人: Privatdozentin Dr.-Ing. Martina Paulsen
• 金额: --
• 依托单位: Arbeitsgruppe Genetik / Epigenetik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5370906?language=en
• 关键词: Identification; regulatory; elements; responsible; genomic

Imprinted genes are preferentially or exclusively expressed from only one of the parental alleles. The silencing of one allele involves epigenetic mechanisms of gene regulation such as DNA methylation and chromatin (histone) modifications. The goal of the proposed project is to identify and characterize genetic and epigenetic elements which control imprinting and to understand their mechanistics. For this purpose we will work on two different gene clusters that are affected by genomic imprinting in mouse: the Beckwith-Wiedemann syndrome (BWS) region on distal chromosome 7 and the Dlk1-Gtl2 region on distal chromosome 12. On chr. 7 the project will focus on the functional analysis of a non-coding transcript residing in a region important for imprinting control in the Kcnq1 gene and on the investigation of imprinting in extraembryonic tissues since here mechanisms of imprinting control appear to be different from embryonic tissues. The Dlk1-Gtl2 region shares similarities with the Igf2-H19 genes in the BWS region. We will identify and study new imprinted genes and differentially methylated elements downstream of Gtl2. This will show if imprinting control in this region shares structural and functional similarities to the BWS region or other imprinted domains. In connection with the functional studies we will pursue genome-wide comparative computational analyses to identify specific sequence and structural features in these imprinted regions and their possible application to characterize other imprinted domains and to identify new imprinted genes.

印迹基因仅由亲本等位基因中的一个优先或专一表达。一个等位基因的沉默涉及基因调控的表观遗传机制，如DNA甲基化和染色质（组蛋白）修饰。该项目的目标是识别和表征控制印迹的遗传和表观遗传因素，并了解其机制。为此，我们将研究受小鼠基因组印记影响的两个不同的基因簇：7号染色体远端贝克威斯-魏德曼综合征（BWS）区域和12号染色体远端Dlk1-Gtl2区域。空空的。该项目将重点分析位于Kcnq1基因印记控制重要区域的非编码转录本的功能，并研究胚胎外组织的印记控制机制，因为这里的印记控制机制似乎与胚胎组织不同。Dlk1-Gtl2区域与BWS区域的Igf2-H19基因具有相似性。我们将鉴定和研究新的印迹基因和Gtl2下游的差异甲基化元件。这将显示该区域的印迹控制是否与BWS区域或其他印迹区域具有结构和功能相似性。在功能研究方面，我们将进行全基因组比较计算分析，以确定这些印迹区域的特定序列和结构特征，并将其应用于表征其他印迹结构域和识别新的印迹基因。