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Human cytomegalovirus (hCMV) immediate early 1 (IE1) protein associates with condensed chromatin of the host cell during mitosis. We have determined the structure of the chromatin-tethering domain (CTD) of IE1 bound to the nucleosome core particle, and discovered that IE1-CTD specifically interacts with the H2A-H2B acidic patch and impairs the compaction of higher-order chromatin structure. Our results suggest that IE1 loosens up the folding of host chromatin during hCMV infections.

Human cytomegalovirus (hCMV) immediate early 1 (IE1) protein associates with condensed chromatin of the host cell during mitosis. We have determined the structure of the chromatin-tethering domain (CTD) of IE1 bound to the nucleosome core particle, and discovered that the specific interaction between IE1-CTD and the H2A-H2B acidic patch impairs the compaction of higher-order chromatin structure. Our results suggest that IE1 loosens up the folding of host chromatin during hCMV infections. DOI: http://dx.doi.org/10.7554/eLife.11911.001, eLife digest Most of the DNA in a cell is tightly wrapped around groups of proteins called histones, which gives the impression of beads on a string. These bead-like structures are called nucleosomes, and interactions between histones in different nucleosomes can link one nucleosome to another, to package the DNA into a very condensed form. Viruses sometimes interact with this condensed DNA; for example, a virus called human cytomegalovirus is known to attach to condensed DNA when cells are preparing to divide. But the consequences of these interactions are not always clear. Now, Fang, Chen et al. have worked out the three-dimensional structure of a protein from the cytomegalovirus while it is attached to a nucleosome. This structure revealed that the viral protein connects to same part of the histones that otherwise helps pull the nucleosomes together. Further experiments then compared how the cytomegalovirus protein attaches to nucleosomes with the interaction between nucleosomes and a similar protein from a different virus. Both viral proteins were seen to interact with the same part of the histone protein, but in different ways. Next, Fang, Chen et al. showed that the DNA is more loosely packed when the cytomegalovirus protein is attached to the nucleosomes. This was not the case for the similar protein from the other virus. The experiments show that small differences in the ways viral proteins interact with condensed DNA can change their effects on DNA packaging. Additionally, these findings may help scientists to better understand how the binding of the cytomegalovirus protein to the nucleosomes might affect this virus’s ability to infect or cause illness in humans. DOI: http://dx.doi.org/10.7554/eLife.11911.002