Using a new measurement technique, Heidelberg researchers have succeeded in tracking interactions between proteins and DNA in the cell nucleus at a resolution of 1/1000 of a second.
Microscopy images after bleaching the fluorescence in a circular or rectangular region. The dark “shadows” represent the bleached proteins that moved as the image was being recorded.
Picture credits: Fabian Erdel and Karsten Rippe
They were able to measure the binding of highly specialised protein complexes that specifically change the spatial structure of the genetic information, thereby controlling the readout of the DNA information. The work of Dr. Karsten Rippe and his team was carried out at the BioQuant Center of Heidelberg University and the German Cancer Research Center.
Their research has demonstrated that the positioning of nucleosomes – complexes of DNA and specialised proteins – is a precisely regulated molecular process. Aberrant regulation can be linked to several types of cancer. The results of these studies were published in the journal PNAS.
In the human genome, the DNA strands are wrapped around specific packaging proteins, the histones. Located between these complexes, called nucleosomes, are histone-free DNA sequences that connect the nucleosomes, much like a pearl necklace. “Activating a gene requires freely accessible DNA. If the corresponding DNA is occluded in the nucleosome, the gene is often turned off”, explains Dr. Rippe.“Hence, the nucleosome positions determine the readout pattern of the DNA sequence. The free DNA between two nucleosomes is more easily accessible than the DNA sequences in a nucleosome.” Molecular machines called chromatin remodelers can use energy to move nucleosomes along the DNA chain. Thus they establish the readout pattern that, along with other factors, determines the active DNA programme of the cell.
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