Objective
Human endogenous retroviruses encompas about 1% of human genome and supposedly can influence expression of the nearby genes causing their disregulation in germ line and somatic cells, producing in particular hereditary diseases and cancer. Recently one of the participants of the project observed the coincidence in positions of the LTRs of human HERV-K retrovirus and a number of genes encoding Zn-finger regulatory proteins (ZNFs) on human chromosome 19. The proposal is aimed at investigation whether the LTRs are involved in the ZNF regulation and in such a way participate in regulatory cascades in normal and tumour human cells. The ZNFs situated on human chromosomes 7 and 19 will be used for the research. The research activities will be divided in three main blocks: The mapping and sequencing of ZNFs and LTRs on chromosome 7. The investigation of the possible roles of the LTRs in evolution of ZNFs regulation by comparison analysis of: LTR situations in vicinities of ZNF genes in different individuals LTR situations in vicinities of ZNFs in human and chimpanzee genomes tissue specificity of ZNFs expression in human and chimpanzees methylation and nuclease sensitivity status of the LTRs in different tissues. Investigation of the participation of the LTRs in the ZNFs regulation in normal and tumour cells, including: identification and quantitative assessment of ZNF mRNAs in normal and tumour cells for ZNF genes containing the LTRs in their vicinities, determination of the functional statuses (methylation, nuclease sensitivity etc.) of LTRs situated near the ZNFs, the inference of correlation between changes in the ZNFs expression and the near situated LTR functional status. The following results are expected to be obtained. Possible functional roles of the LTRs in genome regulation and in particular in Zn-finger gene expression and evolution will be investigated. ZNFs and LTRs will be mapped on human chromosome 7. The comparative analysis of LTR situations in vicinities of ZNF genes in different individuals will be implemented which is of importance for better understanding of the evolutionary origins of the human populations. A comparative analysis of LTR situations in vicinities of ZNF genes in human and chimpanzee genomes will be performed. The results of this comparison will be important for deeper insight into evolution of the endogenous retroviruses. The comparative analyses of tissue specificity of ZNFs expression in human and chimpanzee will be carried out. The investigation of the possible roles of the LTRs in ZNF gene expressions in normal and corresponding tumour cells will be implemented. The results will give new information concerning elements of the genome involved in tumour emergence. The results obtained will be prepared for joint publications in international peer-reviewed journals and presented at international conferences.
Topic(s)
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35037 Marburg
Germany