FIGURE 6.

Model for TLR-4-induced RelB-dependent formation of facultative heterochromatin and transcription silencing of acute proinflammatory genes in the SSI phenotype. This conceptual model is based on this study and components of our previously published work. SSI is initiated when euchromatin is activated by membrane sensors such as TLR4 that couple to NF-κB activation and subsequent binding of p65 and p50 heterodimers to the promoters of a set of acute proinflammatory genes. Subsequent induction of RelB leads to its recruitment and direct binding to G9a. G9a dimethylates H3K9 to which HP1 binds and links to Dnmt3 binding and DNA CpG methylation. Linker histone H1 and HMGB1 (not shown) are recruited and may facilitate remodeling of the nucleosome(s) that “locks” compacted chromatin and stabilizes the p50/RelB/G9a bond.