Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells.

Sarah G Swygert,Cheng-Fu Kao,Dakota R Hunt,Stephanie Portillo-Ledesma,Tamar Schlick,Toshio Tsukiyama,Po-Yen Lin,William S Noble,Dejun Lin

doi:10.7554/elife.72062

Abstract

A longstanding hypothesis is that chromatin fiber folding mediated by interactions between nearby nucleosomes represses transcription. However, it has been difficult to determine the relationship between local chromatin fiber compaction and transcription in cells. Further, global changes in fiber diameters have not been observed, even between interphase and mitotic chromosomes. We show that an increase in the range of local inter-nucleosomal contacts in quiescent yeast drives the compaction of chromatin fibers genome-wide. Unlike actively dividing cells, inter-nucleosomal interactions in quiescent cells require a basic patch in the histone H4 tail. This quiescence-specific fiber folding globally represses transcription and inhibits chromatin loop extrusion by condensin. These results reveal that global changes in chromatin fiber compaction can occur during cell state transitions, and establish physiological roles for local chromatin fiber folding in regulating transcription and chromatin domain formation.

Highlights

The genetic material of eukaryotic cells is organized into a nucleoprotein complex called chromatin, which regulates the accessibility of the underlying sequence to all DNA-dependent processes
Quiescence-specific, basic patch-dependent fiber folding globally represses transcription and inhibits chromatin loop extrusion by condensin. These results demonstrate that genome-wide changes in chromatin fiber folding can occur in a physiologically relevant cell state, and that local fiber compaction can play key roles in the regulation of transcription and chromatin loops
We have previously shown that distal contacts between nucleosomes over 1 kilobase from each other increase in quiescent cells compared to log

Summary

Introduction

The genetic material of eukaryotic cells is organized into a nucleoprotein complex called chromatin, which regulates the accessibility of the underlying sequence to all DNA-dependent processes. Chromatin organization is a highly active area of study, how the chromatin fiber contributes to domain structure and whether or not these levels of chromatin architecture cooperate in transcriptional regulation is unknown To address these questions, we have used Micro-C to map chromosomal interactions genome-wide at single-nucleosome resolution in purified quiescent. Quiescence-specific, basic patch-dependent fiber folding globally represses transcription and inhibits chromatin loop extrusion by condensin These results demonstrate that genome-wide changes in chromatin fiber folding can occur in a physiologically relevant cell state, and that local fiber compaction can play key roles in the regulation of transcription and chromatin loops

Results

Discussion

Methods