<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Epigenetic characterization of the C3(1) SV40T mouse model of human breast cancer"^^ . "Breast cancer is a heterogeneous disease, and various subtypes have been defined at the level\r\nof gene expression and epigenetic modifications, such as DNA methylation. Epigenetic\r\nalterations are attractive candidates for the development of novel biomarkers or as targets for\r\nnew therapeutic approaches. Mouse models allow monitoring of tumor development from early\r\ntime points of initiation to final stages of tumorigenesis, but are often poorly characterized with\r\nrespect to alterations of the epigenetic landscape. Therefore, the aim of this thesis was to\r\ngenerated genome-wide profiles of DNA methylation and histone modifications for the\r\nC3(1)SV40TAg (C3(1)) mouse model of basal-like breast cancer and to investigate the\r\nepigenetic regulation of long noncoding RNAs.\r\nUsing a genome-wide screen with Methyl CpG Immunoprecipitation followed by next generation\r\nsequencing, we identified several thousand regions with recurrent methylation alterations at\r\ndifferent stages of C3(1) tumorigenesis. Differentially methylated genes pointed towards a\r\nluminal progenitor as tumor cell of origin in the C3(1) model, and we confirmed a link between\r\nDNA methylation and gene expression for five of these genes. Comparisons at the level of\r\npromoter methylation revealed general similarity of the C3(1) methylome to human breast\r\ncancer.\r\nGeneration of a chromatin map of the C3(1) model from four histone modifications (H3K4me3,\r\nH3K4me1, H3K27ac, H3K27me3) allowed an integrative investigation of methylation changes at\r\nbreast tissue-specific enhancer regions. We linked tissue-specific alterations of chromatin states\r\nin combination with DNA methylation to changes in the expression of genes with importance for\r\nmammary gland development and breast cancer. These results unveiled a potential involvement\r\nof transcription factors Etv4 (ETS variant 4) and Runx1 (runt related transcription factor 1) in\r\nC3(1) tumorigenesis that might help to understand tumor development in basal-like breast\r\ncancer.\r\nAn emerging theme in epigenetic research is the capacity of long noncoding RNAs (lncRNAs) to\r\nmodulate gene expression by recruitment of gene-silencing or activating complexes. Since\r\nregulation of lncRNAs expression is poorly characterized, we investigated DNA methylation\r\nchanges during carcinogenesis at lncRNA promoters and their influence on neighboring proteincoding\r\ngenes. Exemplarily, we demonstrated coordinated overexpression of Esrp2 (Epithelial\r\nsplicing regulatory protein 2) and the lncRNA Esrp2-as (Esrp2-antisense) in C3(1) tumors that\r\nwas inversely correlated with DNA methylation levels. Knockdown and overexpression of the\r\ntranscripts did not provide evidence for reciprocal regulation of transcript expression. In contrast,\r\nluciferase reporter assays suggested that co-expression of both transcripts is controlled by\r\ndifferential methylation at a common enhancer region. These results are of clinical relevance as\r\nhigh levels of ESRP2 expression in human breast cancer are linked to unfavorable prognosis."^^ . "2017" . . . . . . . "Katharina"^^ . "Heilmann"^^ . "Katharina Heilmann"^^ . . . . . . "Epigenetic characterization of the C3(1) SV40T mouse model of human breast cancer (PDF)"^^ . . . "Thesis_KH_final_180516_backup_2.pdf"^^ . . . "Epigenetic characterization of the C3(1) SV40T mouse model of human breast cancer (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Epigenetic characterization of the C3(1) SV40T mouse model of human breast cancer (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Epigenetic characterization of the C3(1) SV40T mouse model of human breast cancer (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Epigenetic characterization of the C3(1) SV40T mouse model of human breast cancer (Other)"^^ . . . . . . "small.jpg"^^ . . . "Epigenetic characterization of the C3(1) SV40T mouse model of human breast cancer (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #21944 \n\nEpigenetic characterization of the C3(1) SV40T mouse model of human breast cancer\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .