Role of the interaction between LEDGF and MeCP2 in LINE-1 retrotransposition in the brain

LEDGF/p75 has been identified as a host factor of HIV-1 integration in our research group. Recently a protein-protein interaction was detected between LEDGF/p75 and MeCP2, a transcriptional repressor involved in Rett syndrome. In Psip1 KO mice I observed an upregulation in MeCP2 expression in the substantia nigra and CA3 region, confirming a functional link between both proteins. Since MeCP2 represses LINE-1 retrotransposition, we hypothesize that a downregulation of LINE-1 activity may take place in Psip1 KO mice. First, I will characterize the Psip1 KO mice more in detail. Extensive behavioural phenotyping will be performed to determine affected brain areas and functions. Second, I will expand our knowledge on the interaction between LEDGF/p75 and MeCP2 in cell culture. Different assays will be performed to determine which effect LEDGF/p75 has on the expression of MeCP2. Third, the function of LINE-1 in the brain will be further explored. LINE-1 activity will be determined on protein, mRNA and DNA level. Behavioural phenotyping may also provide clues on the function of LINE-1 in the normal mouse brain. This research will result in a better understanding of the functional interaction between MeCP2 and LEDGF/p75. It will also shed light on the function of LINE-1 in the healthy brain.