PDS5A and TOP2B cooperate for chromatin recruitment via CTCF
- 1Howard Hughes Medical Institute, University of Miami, Miami, FL 33136, USA.
- 2Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
- 3Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Abstract
PDS5A, a cohesin regulatory subunit, and topoisomerase IIB (TOP2B), an enzyme resolving DNA topological problems, interact with CTCF and regulate transcription and genome organization. We ascertained that PDS5A and TOP2B are recruited to CTCF-bound chromatin cooperatively and that catalytically active TOP2B increases PDS5A occupancy genome wide. Notably, the amino-terminal 95 to 116 amino acids of CTCF interacts with PDS5A, giving rise to CTCF-PDS5A-TOP2B interaction in vitro and to PDS5A chromatin enrichment via active TOP2B in vivo. PDS5A-TOP2B function together in moderating the resultant gene expression and genome organization. Loss of CTCF (95 to 116 amino acids) led to dysregulated gene expression and mildly reduced chromatin loops. In gliomas, PDS5A and TOP2B expression levels vary, but correlate, contributing to distinctive gene expression patterns. Inducible PDS5A knockdown led to reduced TOP2B occupancy and altered gene expression. Furthermore, PDS5A mediated sensitivity to TOP2 cancer drugs in glioma cells. This functional interaction between PDS5A and TOP2B at CTCF boundaries expands upon the mechanisms affecting gene regulation through genome organization, with implications for glioma therapeutics.
Related
- Uhrf1 loss disrupts CTCF-associated chromatin organization during early mouse embryogenesis
- Chromatin adaptors and TOPBP1 condensates cooperate to organize ATM signaling
- Disease mutations in the PWWP domain of DNMT3A affect chromatin recruitment through multiple mechanisms
- Ctcf deficiency in myofibers induces pathological genome reprogramming toward the spontaneous development of myopathy
- Multiple mechanisms cooperate to control PUF protein FBF-1 and FBF-2 accumulation in Caenorhabditis elegans germline
BibTeX
@article{gonzalezbuendia2026pds5a,
title = {{PDS5A and TOP2B cooperate for chromatin recruitment via CTCF}},
author = {Edgar Gonzalez-Buendia and Havva Ortabozkoyun and Danny Reinberg},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aeg2830},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aeg2830},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - PDS5A and TOP2B cooperate for chromatin recruitment via CTCF
AU - Edgar Gonzalez-Buendia
AU - Havva Ortabozkoyun
AU - Danny Reinberg
PY - 2026
DA - 2026/10/30
JO - Science Advances
DO - 10.1126/sciadv.aeg2830
UR - https://www.science.org/doi/abs/10.1126/sciadv.aeg2830
AB - PDS5A, a cohesin regulatory subunit, and topoisomerase IIB (TOP2B), an enzyme resolving DNA topological problems, interact with CTCF and regulate transcription and genome organization. We ascertained that PDS5A and TOP2B are recruited to CTCF-bound chromatin cooperatively and that catalytically active TOP2B increases PDS5A occupancy genome wide. Notably, the amino-terminal 95 to 116 amino acids of CTCF interacts with PDS5A, giving rise to CTCF-PDS5A-TOP2B interaction in vitro and to PDS5A chromatin enrichment via active TOP2B in vivo. PDS5A-TOP2B function together in moderating the resultant gene expression and genome organization. Loss of CTCF (95 to 116 amino acids) led to dysregulated gene expression and mildly reduced chromatin loops. In gliomas, PDS5A and TOP2B expression levels vary, but correlate, contributing to distinctive gene expression patterns. Inducible PDS5A knockdown led to reduced TOP2B occupancy and altered gene expression. Furthermore, PDS5A mediated sensitivity to TOP2 cancer drugs in glioma cells. This functional interaction between PDS5A and TOP2B at CTCF boundaries expands upon the mechanisms affecting gene regulation through genome organization, with implications for glioma therapeutics.
SN - 2375-2548
ER -