AUTHOR=Sanders Travis J., Ullah Fahad, Gehring Alexandra M., Burkhart Brett W., Vickerman Robert L., Fernando Sudili, Gardner Andrew F., Ben-Hur Asa, Santangelo Thomas J. TITLE=Extended Archaeal Histone-Based Chromatin Structure Regulates Global Gene Expression in Thermococcus kodakarensis JOURNAL=Frontiers in Microbiology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/articles/10.3389/fmicb.2021.681150 DOI=10.3389/fmicb.2021.681150 ISSN=1664-302X ABSTRACT=Histone proteins compact and organize DNA resulting in a dynamic chromatin architecture impacting DNA accessibility and ultimately gene expression. Eukaryotic chromatin landscapes are structured through histone protein variants, epigenetic marks, the activities of chromatin-remodeling complexes, and post-translational modification of histone proteins. In most Archaea, histone-based chromatin structure is dominated by the helical polymerization of histone proteins wrapping DNA into a repetitive and closely gyred configuration. The formation of the archaeal-histone chromatin-superhelix is a regulatory force of adaptive gene expression and is likely critical for regulation of gene expression in all histone-encoding Archaea. Single amino acid substitutions in archaeal histones that block formation of tightly packed chromatin structures have profound effects on cellular fitness, but the underlying gene expression changes resultant from an altered chromatin landscape have not been resolved. Using the model organism Thermococcus kodakarensis, we genetically alter the chromatin landscape and quantify the resultant changes in gene expression, including unanticipated and significant impacts on provirus transcription. Global transcriptome changes resultant from varying chromatin landscapes reveal the regulatory importance of higher-order histone-based chromatin architectures in regulating archaeal gene expression.