Key contributions concern the role of the Polycomb and Trithorax proteins in epigenetic regulation, including their part in development and disease. The laboratory was the first to identify and describe at the molecular level the transgenerational inheritance of epigenetic traits in a complex organism. Additionally, the laboratory has continuously developed new technologies, the best-known being chromatin immunoprecipitation (ChIP) now used worldwide to detect and map the in vivo distribution of chromatin and DNA-associated proteins.
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. The group studied 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. The group applied 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 entailed extensive usage of next generation sequencing (NGS) technologies and development of new algorithms for sequence data analysis. The group worked towards a better understanding how signal transduction mechanisms relay external cellular information to the nucleus and the chromatin level and reprogram cells.