Reading the chromatinized genome

Eukaryotic DNA-binding proteins operate in the context of chromatin, where nucleosomes are the elementary building blocks. Nucleosomal DNA is wrapped around a histone core, thereby rendering a large fraction of the DNA surface inaccessible to DNA-binding proteins. Nevertheless, first responders in DNA repair and sequence-specific transcription factors bind DNA target sites obstructed by chromatin. While early studies examined protein binding to histone-free DNA, it is only now beginning to emerge how DNA sequences are interrogated on nucleosomes. These readout strategies range from the release of nucleosomal DNA from histones, to rotational/translation register shifts of the DNA motif, and nucleosome-specific DNA binding modes that differ from those observed on naked DNA. Since DNA motif engagement on nucleosomes strongly depends on position and orientation, we argue that motif location and nucleosome positioning co-determine protein access to DNA in transcription and DNA repair.

Automated summary

Eukaryotic DNA-binding proteins interact with nucleosomal DNA in the context of chromatin. While nucleosomes make a large fraction of the DNA inaccessible to proteins, certain factors can still bind to DNA sites obstructed by chromatin. Various strategies are employed to read DNA sequences on nucleosomes, such as releasing nucleosomal DNA, shifting DNA motifs, and using nucleosome-specific DNA binding modes. Motif location and nucleosome positioning both play a crucial role in determining protein access to DNA for transcription and repair processes.