Epigenetic and functional changes in differentiation and proliferation induced by BORIS expression

保守转录因子BORIS在小鼠和人体内的主要表达仅限于生殖系细胞。该因子与睾丸中不表达的必不可少且普遍存在的调节因子CTCF相似。与这种正常情况相反，BORIS在许多肿瘤细胞系和肿瘤组织中都有表达。由于CTCF和BORIS结合相同或至少相似的DNA序列，因此在BORIS表达阳性的病理病例中，可以预期这些因子之间的竞争。已发表的实验和自己的初步实验表明，这两种因素在分子功能上存在极大差异，包括BORIS介导的DNA甲基化变化。我们想了解病理性BORIS表达在分子水平上对基因组中所有靶点的影响。一个重要的焦点将是DNA甲基化的变化，它不仅对基因活性起重要作用，而且对基因体中替代启动子的控制也起重要作用。为此，我们将使用带有cre重组酶整合基因和loxP元件的小鼠ES细胞系统来产生Tet调控的BORIS表达。BORIS介导的对胚胎干细胞增殖和分化过程中DNA甲基化的影响将在全基因组范围内进行测试。

The major expression of the conserved transcription factor BORIS in mouse and man is restricted to germ line cells. This factor is paralogous to the essential and ubiquitous regulator CTCF, which is not expressed in testis. In contrast to this normal situation, BORIS expression has been identified in many tumor cell lines and in tumor tissues. Since CTCF and BORIS bind to identical or at least similar DNA sequences, a competition between these factors can be expected in pathological cases positive for BORIS expression. Published and own preliminary experiments show that both factors differ in their molecular function extremely, including BORIS mediated changes in DNA methylation. We would like to understand the consequences of pathological BORIS expression at the molecular level on all target sites in the genome. An important focus will be on the changes on DNA methylation, which plays an important role not only for gene activity, but also for the control of alternative promoters in the gene body. For this we will use the mouse ES cell system with the integrated gene for cre recombinase flanked by loxP elements to generate Tet regulated BORIS expression. BORIS mediated effects on DNA methylation during ES cell proliferation and differentiation will be tested on a genome-wide scale.