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SP19: Steve Hoffmann - Bioinformatics analysis of transcriptional and epigenomic responses to posttranslational modifications

Posttranslational modification (PTMs) of transcription factors (TFs) and histones are critical mechanisms for regulating the genomic activity. For some TFs, chemical alterations of lysines are known to influence the protein localization and affect essential protein-protein interactions as well as promoter and transcription factor binding site (TFBS) affinities. We develop bioinformatic approaches to better investigate the influence of such modifications on genome regulation. In this project, we will develop computational methods to better detect differential binding of TFs as well as differential start site usage. We contribute our wet-lab expertise to measure the impact of various PTMs on TF-binding and isoform-specific expression levels. The computational integration of the ChIP and RNA data within ProMoAge will allow uto better understand the impact of certain PTMs on genome activity and to identify relevant functional networks. Besides, we provide solutions to integrate other layers of information such as DNA methylation systematically. 

 

 

 

Identification of differential TSS usage upon activation of proteins. CAGE-Seq on RNA from MCF-7 cells treated with Nutlin-3a or DMSO solvent control to identify p53-dependent TSS usage. CAGE-Seq data and publicly available p53 ChIP-Seq tracks are displayed using the UCSC Genome Browser. Nutlin-3a treatment induces intronic p53 binding (upper tracks) and strand-specific TSS usage as identified by CAGE-Seq (bottom tracks) in the MDM2. P-values indicate the results of statistical tests under development in the course of this project.