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

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 (ERα) 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 ERα 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 ERα 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 ERα target genes are not required to co-localize in the nucleus.

• Publication year

  2010

• Venue

  PLoS Genetics

• Publication date

  2010-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pgen.1000922PMID 20421946PMCID 2858706
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Estradiol-induced estrogen receptor alpha (ERα) target genes are not required to co-localize in the nucleus.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• Although chromosome territory volume increased after hormone addition, the relative nuclear positions of the chromosome territories remained unaffected.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• Nuclear separation between PGR and CTSD was unchanged by hormone addition and transcriptional activation, with no evidence for allele co-localization.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• TFF1 and GREB1 showed no particular spatial relationship in the nucleoplasm, and their nuclear separation was unchanged after estradiol treatment.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review

• chromosome territories

  nuclear structure, genome organization

  The spatially distinct nuclear regions occupied by individual chromosomes.

  Aliases: chromosomal territories

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• ctsd

  gene

  A cathepsin D gene analyzed as another estrogen-responsive locus in the nucleus.

  Aliases: cathepsin D

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• estradiol

  hormone, treatment

  An estrogen hormone used here to activate transcription in the examined breast epithelial and cancer cells.

  Aliases: E2, estrogen

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• estrogen receptor alpha (erα) target genes

  gene set, molecular target

  Genes whose expression is regulated by estrogen receptor alpha in this experimental system.

  Aliases: ERα target genes, ER-alpha target genes

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• greb1

  gene

  A specific estrogen-responsive gene examined for its nuclear position relative to other loci.

  Aliases: growth regulation by estrogen in breast cancer 1

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• nuclear co-localization

  spatial organization, phenomenon

  The spatial overlap or close shared positioning of genes or alleles within the nucleus.

  Aliases: co-localization, colocalization

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• pgr

  gene

  A progesterone receptor gene analyzed as another estrogen-responsive locus in the nucleus.

  Aliases: progesterone receptor

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review
• tff1

  gene

  A specific estrogen-responsive gene examined for its nuclear position relative to other loci.

  Aliases: trefoil factor 1

  박진우 (dztg5apj7m) extractionB (s683577b42) review배휘동 (872fa5d2c9) reviewimjlk (vdp8mqzes2) review

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