Molecular Cell Paper – Histone binding measured with MST

Our genome is densely packaged in the cell nucleus to protect the fragile DNA molecule and to control its activity. Scientists from the University of Regensburg and Munich discovered a novel RNA-dependent pathway that unpackages the genome and makes it accessible for gene expression. MST was the key method used to elucidate this pathway, as it was used to measure and quantify the affinities of core histone proteins with regulating molecules.

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The genome encoding for all information to build an entire organism is made of DNA. This molecule is a very thin thread of about 1 m in length, consisting of 3*10Λ9 base pairs in humans. The DNA has to fit into a cell nucleus with a diameter that is 100.000 times smaller than the length of the DNA. In order to stow and to protect the fragile DNA molecule inside, it is wrapped around molecular spools consisting of proteins. About 30 million of such spools, arranged like pearls on a string, are required to package the DNA molecule. The pearls on a string undergo further coiling and compacting to safely store DNA that is called chromatin in its packaged form. However, for cell function and daily use, the DNA information of specific genomic regions have to be rendered accessible. Therefore active mechanisms must have evolved to unpackage the genome and allow the readout of the underlying genetic information.

Researchers belonging to the groups of the biochemist Gernot Längst from the University of Regensburg and Axel Imhof a molecular biologist at the LMU in Munich could now show that small RNA molecules regulate the accessibility and structure of the DNA in chromatin. They identified and characterized snoRNAs (a specific class of RNA molecules) as key regulators of chromatin organization. In combination with an RNA and chromatin binding protein, the adapter protein Df31, the RNA binds to specific regions of the genome. This complex interferes with the regular packaging of chromatin and locally decondenses this structure, thereby allowing the readout of the genetic information.

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