Characterizing the molecular architectures of chromatin-modifying complexes.
Eukaryotic cells package their genome in the form of a DNA-protein complex known as chromatin. This organization not only condenses the genome to fit within the confines of the nucleus, but also provides a platform for a cell to regulate accessibility to different gene sequences. The basic packaging element of chromatin is the nucleosome, which consists of 146 base pairs of DNA wrapped around histone proteins. One major means that a cell regulates chromatin structure is by depositing post-translational modifications on nucleosomal histone proteins, and thereby altering internucleosomal interactions and/or binding to different chromatin associated factors. These chromatin modifications are often catalyzed by multi-subunit enzyme complexes, whose large size, sophisticated composition, and inherent conformational flexibility pose significant technical challenges to their biochemical and structural characterization. Multiple structural approaches including nuclear magnetic resonance spectroscopy, X-ray crystallography, single-particle electron microscopy, and crosslinking coupled to mass spectrometry are often used synergistically to probe the overall architecture, subunit organization, and catalytic mechanisms of these macromolecular assemblies. In this review, we highlight several recent chromatin-modifying complexes studies that embodies this multipronged structural approach, and explore common themes amongst them. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman.
['Setiaputra|Dheva T|DT|', 'Yip|Calvin K|CK|']
D000818:Animals D002843:Chromatin D042002:Chromatin Assembly and Disassembly D018360:Crystallography, X-Ray D004247:DNA D004268:DNA-Binding Proteins D006801:Humans D046912:Multiprotein Complexes D019906:Nuclear Magnetic Resonance, Biomolecular
Chromatin-modifying complex Nucleosome Post-translational modifications Nuclear magnetic resonance spectroscopy X-ray crystallography Electron microscopy