Reprogramming Epigenetic Memory
Epigenetics deals with the inheritance of characteristics that are not encoded in the DNA sequence. Epigenetic processes control, for example, the heritability of cell identities, which are encoded in their unique and corresponding gene expression patterns. When cells divide they must retain their identities, a process termed “cellular or transcriptional memory”. However, there are also conditions, such as those during tissue regeneration or in particular environmentally-induced disorders, where identities become reprogrammed and hence cellular memories change.
In the nucleus of a cell, DNA is associated with histones, forming structures termed nucleosomes. Cellular factors including histone modifying enzymes, non-coding RNAs and the DNA methylation machinery play important roles in the establishment of the epigenetic state of a cell. We want to understand at the molecular level how reprogramming of cellular memory occurs. Interplay of specific chromatin modifying proteins from the so-called Polycomb group and the Trithorax group ensure that gene expression patterns are stably and faithfully inherited during DNA replication and mitosis. We apply a systematic approach on a genome-wide scale to study and better understand the epigenetic network of chromatin factors, during normal development and in the context of cellular reprogramming. This entails extensive usage of next generation sequencing (NGS) technologies and development of new algorithms for sequence data analysis. We also want to understand how signal transduction mechanisms relay external cellular information to the nucleus and the chromatin level and reprogram cells. In the future, we would like to be able to use this knowledge to distinctively and heritably alter the fate of cells through external signals in order to generate specific tools for cell-based therapies in regenerative medicine.