Hormone-control regions mediate steroid receptor-dependent genome organization

Area of Science:

• Genomics
• Molecular Biology
• Cancer Research

Background:

• Topologically associating domains (TADs) regulate gene transcription in response to steroid hormones in breast cancer cells.
• Estrogen receptor (ESR1) and progesterone receptor (PGR) binding sites form clusters within these regulatory TADs.

Purpose of the Study:

• To characterize hormone-control regions (HCRs) as units of hormonal gene regulation.
• To investigate the role of HCRs in genome organization and gene transcription modulation by steroid hormones.

Main Methods:

• Identification and characterization of HCRs in T47D breast cancer cells.
• Analysis of ESR1 and PGR binding sites and their interactions within TADs.
• Assessment of HCRs' role in genome organization and transcriptional response to hormones.

Main Results:

• Over 200 HCRs, containing intermingled ESR1 and PGR binding sites, were identified in T47D cells.
• HCRs form stable long-distance inter-TAD interactions and looping structures with promoters, independent of hormone presence.
• Hormone-dependent dynamic modulation of HCR organization and transcriptional responses was observed.

Conclusions:

• Steroid hormone receptors (ESR1, PGR) function as genome organizers, not just transcription factors.
• HCRs act as signaling platforms integrating diverse inputs, leading to complex transcriptional outcomes.
• Receptor expression and hormone signaling dynamically shape genome architecture and gene expression in breast cancer.