Activation of Estrogen-Responsive Genes Does Not Require Their Nuclear Co-Localization

• Published in: PLoS genetics Vol. 6; no. 4; p. e1000922
• Main Authors: Kocanova, Silvia, Kerr, Elizabeth A., Rafique, Sehrish, Boyle, Shelagh, Katz, Elad, Caze-Subra, Stephanie, Bickmore, Wendy A., Bystricky, Kerstin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2010; Public Library of Science (PLoS)
• Subjects: Binding sites; Biochemistry, Molecular Biology; Cell Biology; Cell Biology/Gene Expression; Cell Biology/Nuclear Structure and Function; Cell Line, Tumor; Cell Nucleus; Cell Nucleus - metabolism; Chromosomes; Epithelial Cells; Epithelial Cells - metabolism; Estrogen; Estrogen Receptor alpha; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogens; Estrogens - pharmacology; Female; Gene expression; Genetic aspects; Genetic regulation; Genetics and Genomics/Cancer Genetics; Genetics and Genomics/Chromosome Biology; Genetics and Genomics/Epigenetics; Genetics and Genomics/Nuclear Structure and Function; Humans; Life Sciences; Molecular Biology; Molecular Biology/Post-Translational Regulation of Gene Expression; Neoplasm Proteins; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Oncology/Breast Cancer; Physiological aspects; Receptors; Thermal cycling; Trefoil Factor-1; Tumor Suppressor Proteins; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; France; United Kingdom
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000922

The spatial organization of the genome in the nucleus plays a role in the regulation of gene expression. Whether co-regulated genes are subject to coordinated repositioning to a shared nuclear space is a matter of considerable interest and debate. We investigated the nuclear organization of estrogen receptor alpha (ERalpha) target genes in human breast epithelial and cancer cell lines, before and after transcriptional activation induced with estradiol. We find that, contrary to another report, the ERalpha target genes TFF1 and GREB1 are distributed in the nucleoplasm with no particular relationship to each other. The nuclear separation between these genes, as well as between the ERalpha target genes PGR and CTSD, was unchanged by hormone addition and transcriptional activation with no evidence for co-localization between alleles. Similarly, while the volume occupied by the chromosomes increased, the relative nuclear position of the respective chromosome territories was unaffected by hormone addition. Our results demonstrate that estradiol-induced ERalpha target genes are not required to co-localize in the nucleus.