Biology subjects

Swygert, S. G.

Publications and source records attributed to Swygert, S. G..

3 recordsLinked to original sources

bioRxiv2026

Asymmetric condensin loop extrusion is regulated by RPA-coated single-stranded DNA in quiescent cells

SMC complexes influence virtually all DNA-dependent processes by organizing the genome via the process of loop extrusion. Although transcription has been implicated in regulating SMC complex function, the underlying mechanisms remain unclear. Further, the directionality of loop extrusion observed in biochemical experiments has been difficult to reconcile with the chromatin condensation observed in cells. Here, we use a quiescent yeast model to uncover the relationship between condensin loop extrusion and transcription. Condensin gradually relocates to transcribed gene promoters during quiescence entry, allowing us to dissect condensin targeting mechanisms temporally. Through targeted degradation experiments, we discover that topological stress generated by transcription leads to single-stranded DNA accumulation at promoters, and that these RPA-bound regions are loading sites and extrusion barriers for condensin. We further use a condensin mutant to determine that condensin extrudes loops asymmetrically in cells. We propose that antagonism by RPA universally regulates SMC complex function.

molecular biology↗

bioRxiv2020

Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells

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.

molecular biology↗

bioRxiv2018

Condensin-dependent chromatin condensation represses transcription globally during quiescence

Quiescence is a stress-resistant state in which cells reversibly exit the mitotic cell cycle and suspend most cellular processes. Quiescence is essential for stem cell maintenance and its misregulation is implicated in tumor formation. One of the conserved hallmarks of quiescent cells, from Saccharomyces cerevisiae to humans, is highly condensed chromatin. Here, we use Micro-C XL to map chromatin contacts at single-nucleosome resolution genome-wide to elucidate mechanisms and functions of condensed chromatin in quiescent S. cerevisiae cells. We describe previously uncharacterized chromatin domains on the order of 10-60 kilobases that in quiescent cells are formed by condensin-mediated chromatin loops. Conditional depletion of condensin prevents chromatin condensation during quiescence entry and leads to widespread transcriptional de-repression. We further demonstrate that condensin-dependent chromatin compaction is conserved in quiescent human fibroblasts. We propose that condensin-dependent condensation of chromatin represses transcription throughout the quiescent cell genome.

molecular biology↗