Two-way feedback between chromatin compaction and histone modification state explains S. cerevisiae heterochromatin bistability.

Chromatin is the complex formed by proteins, including histones, and DNA to form chromosomes. Specific chromatin structures and states are thought to be key factors regulating transcription. A common view proposes that histone modifications activate or inhibit transcription either via specific activation or inhibition of RNA polymerase binding/elongation at a locus, or by expanding/compacting the locus, thereby modulating its accessibility to many macromolecules. In this work, we elucidated a broader hypothesis that chromatin compaction may both inhibit transcription, and feedback via silencing proteins to remove histone modifications that further control chromatin compaction and correlate with gene activity. We developed a model incorporating these ideas and showed that it explains quantitative experimental data for a silent locus in budding yeast.