Table 4.

Role of cohesin in steroid hormone response pathways

OrganismSteroid hormoneEvidence of role for cohesinReference
DrosophilaEcdysoneCohesin is necessary for EcR-dependent axon pruning in the mushroom body.74
Ecdysone-responsive genes have high levels of cohesin binding.76, 77
Cohesin regulates EcR at the transcriptional level.75–77
Cleavage of cohesin affects expression of ecdysone-dependent genes. Changes in ecdysone-responsive genes occur before EcR levels can be affected, indicating that cohesin's role in ecdysone gene response is more than solely regulating EcR levels.75
HumanEstrogenCohesin is required for estrogen-mediated reentry into the cell cycle (G0/G1–S-phase transition).88
Global analysis of cohesin binding to chromatin shows that cohesin colocalizes with the ER at many sites throughout the genome.88
In ER-positive MCF7 breast cancer cells, cohesin binding is positively correlated with estrogen-regulated genes.88
Genome-wide analysis of chromatin interactions throughout the genome identified ER-anchored chromatin loops in estrogen-responsive genes.89
Cohesin binding is enriched at sites involved in ER-mediated chromatin interactions, suggesting that cohesin may stabilize these loops.88, 89
An extensive shRNA screen revealed that downregulation of individual subunits of cohesin increased survival of MCF-7 breast cancer cells exposed to tamoxifen over an extended period.136
Clones of ER-positive ZR-751 breast cancer cells expressing ectopic RAD21 exhibit reduced sensitivity to the antiestrogen ICI 182780 or to tamoxifen in an agar growth assay.139
MCF7 cells with acquired resistance to tamoxifen have 1.6-fold higher expression of RAD21 and 3-fold lower expression of PDS5B than tamoxifen-sensitive cells.138
AndrogenPDS5b is required for androgen-mediated proliferative arrest in G0/G1.116
AR mediates looping of androgen-regulated genes.123, 125
PDS5b is induced by levels of androgens that inhibit cell growth.114
Rad21 levels are higher and PDS5b levels are lower in androgen-independent vs. androgen-dependent prostate cancer cell lines.160