Figure 2.

Host epigenetic mechanisms affected by pathogens. Pathogens use a wide variety of mechanisms to modulate host chromatin, as discussed further in Molecular Mechanisms of Epigenetic Modification and summarized in Table 1. To prevent chromatin remodeling and, therefore, maintain a silenced state, M. tuberculosis secretes LpqH lipoprotein, which binds to SWI/SWF remodeling complexes and blocks their function. L. monocytogenes regulates chromatin state via the effector protein LntA, which recruits heterochromatin regulator BAHD1 to recruit heterochromatin proteins and induce formation of heterochromatin. HIV, on the other hand, uses vpr protein to target p300/HAT complexes, causing them to dissociate from chromatin. Alternatively, some pathogens express proteins that directly bind DNA to induce transcription or prevent it. Hepatitis C virus expresses NS5A, which binds promoter regions of host genes. S. flexneri prevents transcription by sequestering host transcription factors, such as the Rb tumor-suppressor proteins. Chromatin state is also regulated by histone post-translational modifications, which can be modulated through manipulation of host enzymes or directly through secreted effector enzymes. For example, S. flexneri modulates the phosphorylation of histone H3S10 through the activity of OspF, a secreted phosphothreonine lyase. OspF removes phosphate groups from Erk2 and p38, two members of the MAPK pathway, which prevents MAPK-dependent H3S10 phosphorylation. Gray line, DNA; red line, silenced promoter; red circles, histone PTMs. Me, cytosine methylation.