1 Computational and RNA Biology, Department of Biology, Faculty of Science, Københavns Universitet2 Bio-Informatics Group, BRIC Research Groups, BRIC, Københavns Universitet3 RIKEN4 Wayne State University5 German Center for Neurodegenerative Diseases (DZNE)6 University of British Columbia7 unknown8 Computational and RNA Biology, Department of Biology, Faculty of Science, Københavns Universitet9 RIKEN10 Wayne State University11 University of British Columbia
BACKGROUND: Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes RESULTS: Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum CONCLUSIONS: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome.