The Structural Basis of Gene Regulation for DNA Organized as Chromatin

Abstract

DNA in the nucleus of eukaryotic cells is organized in chromatin, a nucleoprotein complex containing roughly half DNA and half protein. The nucleosome is the underlying DNA packaging element in chromatin, repeating approximately every 200 base pairs over essentially the entire genome. Our crystal structure of the nucleosome core particle explains in atomic detail how DNA in its first level of organization is kept untangled by the histone protein octamer and clarifies the unique role the nucleosome plays in the expression of genetic information. Dynamic assembly and disassembly of the chromatin fiber, the higher-order arrangement of nucleosomes, most probably defines the crucial step in controlling DNA access enabling efficient regulation of gene readout. Multiprotein complexes, here designated 'regulasomes', are bound at specific sites within chromatin to coalesce the histone modification and chromatin remodeling protein assemblies that affect the stability and structure of the chromatin fiber. The formation of a particular regulasome depends on cooperative interaction between the transcription factor proteins comprising it, and on their interaction with specific DNA sequences. Our crystal structures of selected transcription factor complexes bound to their target site DNA contribute to the structural basis of how specificity of gene expression is achieved.