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

点击翻译按钮获取中文摘要

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.