Structural insights into the interaction between transcription factors and the nucleosome.

In eukaryotic cells, DNA interacts with two main types of binding proteins: transcription factors and histones. Histones form the core of nucleosomes and display weak sequence preference owing to differences in bendability of different DNA sequences. By contrast, the affinity of transcription factors is highly dependent on DNA sequence - all sequences are bound with moderate affinity, but only few specific sequences are bound more tightly via molecular recognition of the DNA bases. Transcription factors can interact with nucleosomes directly by recognizing nucleosome-associated DNA and also indirectly by recruiting histone-modifying enzymes and nucleosome remodelers. These interactions result in sequence-dependent formation of a pattern of open and closed chromatin, where specific positions are occupied by transcription factors, histone-modifying enzymes, and modified histones. These patterns are then recognized by large DNA-associated macromolecular complexes such as cohesin and RNA polymerase II, which are involved in regulation of higher-order chromatin structure and transcription, respectively. Here, we review recent work that has provided structural and mechanistic insight into the interactions between all these classes of DNA-associated proteins.