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PNAS publishes paper on chromatin remodeling

The paper "DNA sequence- and conformation-directed positioning of nucleosomes by chromatin-remodeling complexes" by Karsten Rippe, Anna Schrader, Philipp Riede, Ralf Strohner, Elisabeth Lehmann and Gernot Längst has been published in the Proceedings of the National Academy of Sciences of the USA (PNAS) on September 24, 2007. This work continues the fruitful collboration with the group of Gernot Längst in Regensburg on the mechanism and function of the ATP-driven molecular machines that can translocate nucleosomes along the DNA as described in press release below.

Rippe, K., Schrader, A., Riede, P., Strohner, R., Lehmann, E., and Längst, G. (2007). DNA sequence- and conformation-directed positioning of nucleosomes by chromatin-remodeling complexes. Proc. Natl. Acad. Sci. USA, advance online publication, 24 September 2007. Abstract | Reprint (1.4 MB pdf file).

Reading between the lines - new words in the book of DNA

How does a cell regulate the access to the information encoded in its DNA? Scientists from the University of Regensburg and the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have identified mechanisms, by which molecular machines read out the DNA sequence to regulate the DNA accessibility for other protein factors.

All the cells of the human body contain essentially the same DNA sequence and with it the identical genetic information. The DNA sequence encodes the complete construction and maintenance plan of the organism. However, each cell “reads” only part of the DNA “book”, and uses only some of its plans and recipes to exert specific functions. But how does a given cell select the appropriate DNA program that makes it for example a muscle cell, a liver cells or a skin cell? One of the sophisticated mechanisms involved in this process is the packaging of the DNA in the cell nucleus into a structure called “chromatin” (the term originates from the Greek word “chroma”, i. e. color, because it can be easily stained for imaging by light microscopy): The negatively charged DNA is wrapped around small positively charged histone proteins to form a chain of globular complexes termed “nucleosomes” that are connected by segments of protein free “linker DNA”. DNA within the nucleosome is less accessible for other protein factors than linker DNA. Hence, the positions of the nucleosomes determine whether certain DNA sequences are in the more easily accessible DNA linker region between nucleosomes or are masked by histone-DNA interactions. Thus, differences in nucleosome position, in conjunction with other regulatory mechanisms, decide whether genes are active or inactive and different cellular functions can be selected. This is a dynamic process. Energy consuming molecular machines that are referred to as “chromatin remodeling complexes” can move nucleosomes along the DNA chain to switch between “on” and “off” states of the DNA.

In a recent study researchers of the University of Regensburg in the group of Gernot Längst together with Karsten Rippe from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have revealed a mechanism, by which chromatin remodeling complexes “read” the DNA sequence to position nucleosomes at different DNA sites. On top of the “genetic code”, which relates the DNA sequence with the protein sequence, a “chromatin remodeling code” seems to link DNA sequence and nucleosome positions. As a human cell is estimated to contain hundreds of different chromatin remodelers these could form a regulatory network, in which their targeting to certain chromatin regions is involved in selecting the gene expression program of a cell.
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