Corepressor subnuclear organization is regulated by estrogen receptor via a mechanism that requires the DNA-binding domain

Ty C. Voss, Ignacio A. Demarco, Cynthia F. Booker, Richard Day

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The restriction of transcription factors to certain domains within the cell nucleus must serve an important regulatory function. The silencing mediator of retinoic acid and thyroid hormone (SMRT) and other members of the corepressor complex are enriched in spherical intranuclear foci, and repress estrogen receptor alpha (ERα)-dependent transcriptional activity. When fluorescent protein (FP)-labeled SMRT and ERα were co-expressed, the proteins co-localized. The subnuclear organization and positioning of the complexes, however, depended on the ligand state of the receptor. Automated image analysis was used to quantify the ERα-dependent change in SMRT organization in randomly selected living cell populations. The results demonstrate that the subnuclear positioning of SMRT is influenced by the ligand-bound ERα, and this activity is dependent on the ratio of the co-expressed ERα and SMRT. A deletion mutant of ERα showed that the receptor DNA-binding domain was necessary for the ligand-dependent positioning of SMRT. These results define important organizational mechanisms that underlie nuclear receptor regulation of gene expression.

Original languageEnglish (US)
Pages (from-to)33-47
Number of pages15
JournalMolecular and Cellular Endocrinology
Volume231
Issue number1-2
DOIs
StatePublished - Feb 28 2005
Externally publishedYes

Fingerprint

Co-Repressor Proteins
Estrogen Receptor alpha
Estrogen Receptors
Tretinoin
Thyroid Hormones
DNA
Ligands
Nuclear Receptor Co-Repressor 2
Thyroid Hormone Receptors alpha
Cells
Gene Expression Regulation
Cytoplasmic and Nuclear Receptors
Cell Nucleus
Gene expression
Image analysis
Proteins
Transcription Factors
Population

Keywords

  • Estrogen receptor alpha
  • Fluorescence microscopy
  • Green fluorescent protein
  • Nuclear corepressor
  • Nuclear structure
  • SMRT
  • Transcriptional regulation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Corepressor subnuclear organization is regulated by estrogen receptor via a mechanism that requires the DNA-binding domain. / Voss, Ty C.; Demarco, Ignacio A.; Booker, Cynthia F.; Day, Richard.

In: Molecular and Cellular Endocrinology, Vol. 231, No. 1-2, 28.02.2005, p. 33-47.

Research output: Contribution to journalArticle

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