Identification of regulatory elements responsible for genomic imprinting in mammals

印记基因仅从亲本等位基因中的一个优先或排他地表达。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记的遗传和表观遗传因素，并了解其机制。为了这个目的，我们将在两个不同的基因簇，受基因组印记在小鼠：贝克威-威德曼综合征（BWS）的远端7号染色体上的区域和远端12号染色体上的Dlk 1-Gtl 2区域。在第7章，该项目将集中于对Kcnq 1基因中对印迹控制重要的区域中的非编码转录本的功能分析，以及对胚外组织中印迹的研究，因为这里的印迹控制机制似乎与胚胎组织不同。Dlk 1-Gtl 2区域与BWS区域中的Igf 2-H19基因具有相似性。我们将确定和研究新的印迹基因和差异甲基化的元件下游的Gtl 2。这将显示该区域中的印迹控制是否与BWS区域或其他印迹结构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及其可能的应用，以表征其他印迹结构域，并确定新的印迹基因。

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.