2025/01/01 by Luis E. Abatti, Zoe E. Gillespie, Patricia Lado‐Fernández +2 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Genomics and Chromatin Dynamics #Estrogen and related hormone effects #Epigenetics and DNA Methylation
paper · pdf · doi:10.1139/bcb-2024-0287
openalex publication_date 2025/01/01 · openalex created_date 2025/02/27 · openalex updated_date 2026/07/31
Estrogen (E2) regulates the differentiation and proliferation of mammary progenitor cells by modulating the transcription of multiple genes. One of the genes that is downregulated by E2 is SOX2, a transcription factor associated with stem and progenitor cells that is overexpressed during breast tumourigenesis. To elucidate the mechanisms underlying E2-mediated SOX2 repression, we investigated epigenome and transcriptome changes following short- and long-term E2 exposure in breast cancer cells. We found that short-term E2 exposure reduces chromatin accessibility at the downstream SOX2 SRR134 enhancer, decreasing SOX2 expression. In contrast, long-term E2 exposure completely represses SOX2 transcription while maintaining accessibility at the SRR124–134 enhancer cluster, keeping it poised for reactivation. This repression was accompanied by widespread epigenome and transcriptome changes associated with commitment towards a more differentiated and less invasive luminal phenotype. Finally, we identified a role for the transcription factor NFIB in this process, suggesting it collaborates with the estrogen receptor to mediate SOX2 repression and genome-wide epigenome accessibility changes.