Electrostatics of DNA compaction in viruses, bacteria and eukaryotes: functional insights and evolutionary perspective

Acetylation of histone H4 on lysine 16 (H4-K16Ac) is a prevalent and reversible posttranslational chromatin modification in eukaryotes. To characterize the structural and functional role of this mark, we used a native chemical ligation strategy to generate histone H4 that was homogeneously acetylated at K16. The incorporation of this modified histone into nucleosomal arrays inhibits the formation of compact 30-nanometer-like fibers and impedes the ability of chromatin to form cross-fiber interactions. H4-K16Ac also inhibits the ability of the adenosine triphosphate-utilizing chromatin assembly and remodeling enzyme ACF to mobilize a mononucleosome, indicating that this single histone modification modulates both higher order chromatin structure and functional interactions between a nonhistone protein and the chromatin fiber.

Emerging models of the bacterial nucleoid show that nucleoid-associated proteins (NAPs) and transcription contribute in combination to the dynamic nature of nucleoid structure. NAPs and other DNA-binding proteins that display gene-silencing and anti-silencing activities are emerging as key antagonistic regulators of nucleoid structure. Furthermore, it is becoming clear that the boundary between NAPs and conventional transcriptional regulators is quite blurred and that NAPs facilitate the evolution of novel gene regulatory circuits. Here, NAP biology is considered from the standpoints of both gene regulation and nucleoid structure.