Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells (ChIP-Seq)

Determining the conformation of chromatin in cells at the nucleosome level and its relationship to cellular processes has been a central challenge in biology. We show that in quiescent yeast, widespread transcriptional repression coincides with the local compaction of chromatin fibers into structures that are less condensed and more heteromorphic than canonical 30-nanometer forms. Acetylation or substitution of H4 tail residues decompacts fibers and leads to global transcriptional de-repression. Fiber decompaction also increases the rate of loop extrusion by condensin. These findings establish a role for H4 tail-dependent local chromatin fiber folding in regulating transcription and loop extrusion in cells. They also demonstrate the physiological relevance of canonical chromatin fiber folding mechanisms even in the absence of regular 30-nanometer structures. Overall design: Examination of binding of histone H3, penta-acetylated histone H4 tail, Hho1, RNA Polymerase II subunit Rpb3, and condensin subunit Brn1 in log and quiescent cells with wildtype backgrounds, bearing various histone H4 mutations, or treated with the histone decetylase inhibitor TSA or the transcriptional inhibitor phenanthroline.