Highlights 2010

In 2010, scientists at the centre published 34 peer-reviewed papers of which 24 have scientists from the centre as first and/or last author. Three of these will be highlighted here:

The first paper came out in Nature in January (Pasini et al, Nature 2010). The presented results contribute significantly to our knowledge of how the development of embryonic stem cells is regulated. The scientists demonstrated that the protein JARID2 plays an essential role for the binding of the Polycomb group (PcG) proteins to target genes and, consistent with this, for the proper differentiation of embryonic stem cells as well as for normal development.

The results not only extend our understanding of basal mechanisms in cell development. They also open for a whole new view on diseases like cancer. The growth of normal, specialised cells is only limited whereas cancer cells are characterised by uncontrollable growth and a lacking specialisation – and especially the lacking specialisation is a consequence of too much JARID2 in the cells.

The second paper (Gehani et al, Mol Cell 2010) presents results showing how certain mole- cules and chemicals, e.g. from pollution, tobacco or toxins from bacteria, can stress the cells to produce proteins they normally would not produce. The scientists have studied the protein complex PRC2, which under normal conditions prevents the production of unwanted proteins by methylating the histones. But in response to external stress, the protein MSK will in a similar way phosphorylate the histones – and this blocks the effect of the methylations. While the methylations prevent the reading of the genes, the phosphorylations make the genes acces- sible to reading, and thereby initiate a production of unwanted proteins.

During early development but also later on in life, it is essential that the “right” proteins are produced at the right time in the different cell types. Does this not happen, it may have serious consequences, not only for the individual cell, but for both development and function of entire organs and tissues. Similarly, polluting chemicals may induce normal cells to sudden abnormal changes due to the production of the unwanted proteins.

In the third paper (Kleine-Kohlbrecher et al, Mol Cell 2010) the scientists presented results showing that mutations in the gene PHF8 lead to the development of X-linked mental retardation: If PHF8 is mutated and its function therefore inactivated, it cannot contribute to the activation of genes required for normal brain function. Furthermore, the scientists demon- strated how three genes on the X-chromosome, PHF8, ZNF711 and JARID1C, interact in patients with the syndrome, which affects around 1 out of 600 men worldwide. The identifi- cation of new genes and the understanding of their function will be significant for diagnosis and therapy of patients with mental retardation as well as for our understanding of the devel- opment of the brain.