Higher-order chromatin organization defines Progesterone Receptor and PAX2 binding to regulate estradiol-primed endometrial cancer gene expression
- la Greca, Alejandro Damián
- Bellora, Nicolás
- Le Dily, Francois
- Jara, Rodrigo Agustin
- Quilez Oliete, Javier
- Villanueva, José Luis
- Vidal, Enrique
- Merino, Gabriela Alejandra
- Fresno Rodríguez, Cristóbal
- Tarifa Reischle, Inti Carlos
- Vallejo, Griselda
- Vicent, Guillermo P.
- Fernandez, Elmer Andres
- Beato, Miguel
- Saragueta, Patricia Esther
DOIAbstract
Estrogen (E2) and Progesterone (Pg), via their specific receptors (ER and PR respectively), are major determinants in the development and progression of endometrial malignancies. Here, we have studied how E2 and the synthetic progestin R5020 affect genomic functions in Ishikawa endometrial cancer cells. Using ChIPseq in cells exposed to the corresponding hormones, we identified cell specific binding sites for ER (ERbs) and PR (PRbs), which mostly correspond to independent sites but both adjacent to sites bound by PAX2. Analysis of long-range interactions by Hi-C showed enrichment of regions co-bound by PR and PAX2 inside TADs that contain differentially progestin-regulated genes. These regions, which we call “progestin control regions” (PgC...
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