How sensitivity to DNA methylation can limit transcription factor binding

Transcription factors only bind a minority of their motifs in large mammalian genomes. One potential explanation is that many motifs are not accessible for binding due to the action of chromatin and DNA methylation. We are using mammalian stem cell models to understand this important interplay between gene regulation, chromatin structure and DNA methylation. We study the dynamics of the epigenome and test regulatory models in cellular models by genetic perturbation and genome editing approaches.

I will discuss our recent efforts in understanding how the sensitivity to DNA methylation can limit transcription factor binding in the context of the cell and how TFs rely on specific chromatin remodelers for access to their binding sites.

Dirk Schübeler is a Senior Group Leader and Co-Director of the Friedrich Miescher Institute for Biomedical Research (FMI) in Basel, Switzerland. He received a Ph.D. from the Technical University in Braunschweig, Germany and is an adjunct Professor of the University of Basel.

Dirk Schübeler’s research focuses on understanding how chromatin states are generated and how they contribute to the regulation of transcription and replication. His group has pioneered approaches to measure DNA methylation, histone modifications and DNA replication at the level of the genome and to combine these with functional assays. The group has identified recruitment mechanism for readers and writers of DNA methylation towards a better understanding of the information flow that generates and reads a chromatinized genome. In more recent work his group aims to define how transcription factors respond and modify chromatin. Dirk Schübeler is a member of EMBO and has received several awards, including the Friedrich Miescher Prize of the Swiss Society for Biochemistry and the Novartis VIVA award.

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Matt Humphries
Babraham Institute