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Molecular controller switches off genetic material
Genetic material has many inactive sections that are of major importance for the stability of the chromosomes. The HP1 protein takes on key control function in this process, by completely switching off the genetic material. Researchers working together with Prof. Sebastian Hiller from the Biozentrum of the University of Basel and Prof. Marc Bühler from the Friedrich Miescher Institute for Biomedical Research (FMI) show now in the latest issue of Molecular Cell how this dynamic process operates at a molecular level.
Molecular model of how the check-point protein HP1 intercepts unwanted RNA transcripts (green: HP1 binds RNA; yellow: unbound HP1).
The genetic material in the cell has both active and inactive segments. While the genes in the active areas are able to be read like an open book, the inactive regions remain under lock and key. These highly conserved and compacted areas on genetic material are important for gene regulation as well as for the stability and correct distribution of chromosomes during cell division. They are characterized by biochemical changes in the genetic material and in the DNA-binding proteins, the histones. However, even in the inactive regions, the deactivating mechanism does not always function perfectly. To guarantee the inactivation, there is an additional molecular controller - the HP1 protein.
Protein HP1 mediates DNA inactivation
HP1 binds to marked histone proteins and shuts down the genes in this section by tightly packing the DNA. The structural biologist Prof. Sebastian Hiller and his team at the Biozentrum together with Prof. Marc Bühler’s team at the FMI demonstrate how this dynamic process works at a molecular level with a combination of NMR and cell biology using yeast as a model organism for human cells. They could show that the role of watchdog is not taken by just a single HP1 protein, but by a collective of such proteins, which bind to the histone in a continuous relay. In so doing, HP1 intercepts unwanted RNA transcripts of the switched off genetic material and escorts these molecules to the degrading machinery of the cell. Simultaneously, a new HP1 occupies the vacated space at the histone. This continual changeover guarantees that the inactivated regions remain permanently inaccessible and that RNA transcripts of genes from this section are continuously destroyed.
Dynamic interactions
The biophysical measurements show how the HP1 dynamically monitors the chromatin situation. This dynamic setup allows the cells to control the inactivation on two different levels at the same time. At present, the findings are at the pure fundamental research level. The complete mechanism, however, provides insight into the importance of HP1, which has been conserved throughout evolution and is also found in humans. “Therefore, in the future we would like to gain a better understanding of how the protein functions in humans, and to investigate its structure in greater detail,” explains the structural biologist Hiller.
Original Article:
Claudia Keller, Ricardo Adaixo, Rieka Stunnenberg, Katrina J Woolcock, Sebastian Hiller and Marc Bühler (2012). HP1Swi6 mediates the recognition and destruction of heterochromatic RNA transcripts. Molecular Cell; Published online June 7th, 2012
Contact: Communications, Katrin Bühler