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Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
Activation of estrogen-responsive genes does not require their nuclear co-localization
Silvia Kocanova1, Elizabeth A Kerr, Sehrish Rafique
1Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse - UPS, Toulouse, France.
Plos Genetics
|April 28, 2010
Summary
Estrogen receptor alpha (ERalpha) target genes do not co-localize in the nucleus after estradiol activation. This study finds no coordinated repositioning of these genes, challenging previous notions of genome organization for gene regulation.
Area of Science:
- Genomics
- Molecular Biology
- Cell Biology
Background:
- Nuclear genome organization influences gene expression regulation.
- The spatial arrangement of co-regulated genes and their potential coordinated movement to shared nuclear compartments is a key area of research and debate.
Purpose of the Study:
- To investigate the nuclear organization of estrogen receptor alpha (ERalpha) target genes in human breast cells.
- To determine if transcriptional activation by estradiol induces coordinated repositioning and co-localization of these ERalpha target genes.
Main Methods:
- Analysis of nuclear organization of ERalpha target genes (TFF1, GREB1, PGR, CTSD) in human breast epithelial and cancer cell lines.
- Assessment of gene distribution and nuclear separation before and after estradiol-induced transcriptional activation.
Main Results:
- ERalpha target genes TFF1 and GREB1 showed no specific spatial relationship to each other in the nucleoplasm.
- Nuclear separation between ERalpha target genes (TFF1, GREB1, PGR, CTSD) remained unchanged upon hormone addition and transcriptional activation.
- No evidence of allele co-localization was observed.
- Chromosome territories' relative nuclear positions were unaffected by hormone addition, despite an increase in occupied nuclear volume.
Conclusions:
- Estradiol-induced ERalpha target genes do not require co-localization within the nucleus for their function.
- The spatial organization of these specific target genes is not dynamically altered to facilitate co-regulation upon activation.
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