Human FACT complex coordinates cohesin and transcription on chromatin
- 1MRC Laboratory of Medical Sciences
Abstract
The spatial organisation of eukaryotic genomes is critical for coordinating DNA-dependent processes such as transcription and replication. Cohesin contributes to this organisation by extruding chromatin loops; however, how cohesin achieves processive translocation along nucleosome-dense chromatin in vivo remains poorly understood. Here, we identify the histone chaperone FACT as a regulator of cohesin dynamics in human cells. We show that the FACT subunit SUPT16H colocalises and interacts with cohesin on chromatin. Depletion of FACT impairs cohesin translocation from its loading sites, leading to reduced chromatin looping and decreased boundary strength of topologically associating domains (TADs), as revealed by Hi-C. In addition, FACT depletion results in the accumulation of cohesin within gene bodies that are not engaged in loop formation, which is associated with reduced transcription. Importantly, degradation of cohesin in FACT-depleted cells restores transcriptional output, indicating that cohesin mislocalisation underlies this effect. Together, these findings demonstrate that FACT facilitates cohesin translocation along chromatin, promoting efficient loop extrusion while preventing its aberrant accumulation within transcribed regions. This work provides mechanistic insight into how chromatin structure modulates cohesin function to coordinate genome organisation with transcription in mammalian cells.
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BibTeX
@misc{garcialuis2026human,
title = {{Human FACT complex coordinates cohesin and transcription on chromatin}},
author = {J. Garcia-Luis and A. Canela and V. Malysheva and T. Natsume and M. M. Karimi and M. Kanemaki and M. Spivakov and L. Aragon},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.754922},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.754922v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Human FACT complex coordinates cohesin and transcription on chromatin
AU - J. Garcia-Luis
AU - A. Canela
AU - V. Malysheva
AU - T. Natsume
AU - M. M. Karimi
AU - M. Kanemaki
AU - M. Spivakov
AU - L. Aragon
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.754922
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.754922v1
AB - The spatial organisation of eukaryotic genomes is critical for coordinating DNA-dependent processes such as transcription and replication. Cohesin contributes to this organisation by extruding chromatin loops; however, how cohesin achieves processive translocation along nucleosome-dense chromatin in vivo remains poorly understood. Here, we identify the histone chaperone FACT as a regulator of cohesin dynamics in human cells. We show that the FACT subunit SUPT16H colocalises and interacts with cohesin on chromatin. Depletion of FACT impairs cohesin translocation from its loading sites, leading to reduced chromatin looping and decreased boundary strength of topologically associating domains (TADs), as revealed by Hi-C. In addition, FACT depletion results in the accumulation of cohesin within gene bodies that are not engaged in loop formation, which is associated with reduced transcription. Importantly, degradation of cohesin in FACT-depleted cells restores transcriptional output, indicating that cohesin mislocalisation underlies this effect. Together, these findings demonstrate that FACT facilitates cohesin translocation along chromatin, promoting efficient loop extrusion while preventing its aberrant accumulation within transcribed regions. This work provides mechanistic insight into how chromatin structure modulates cohesin function to coordinate genome organisation with transcription in mammalian cells.
ER -