Nuclear compartmentalization of N-CoR and its interactions with steroid receptors

Yin Wu, Hisaya Kawate, Keizo Ohnaka, Hajime Nawata, Ryoichi Takayanagi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The repression mechanisms by the nuclear receptor corepressor (N-CoR) of steroid hormone receptor (SHR)-mediated transactivation were examined. Yellow fluorescent protein (YFP)-N-CoR was distributed as intranuclear discrete dots, while coexpression of androgen receptor (AR), glucocorticoid receptor a, and estrogen receptor α ligand-dependently triggered redistribution of YFP-N-CoR. In fluorescence recovery after photobleaching analysis, mobility of the N-CoR was reduced by 5α-dihydrotestosterone (DHT)-bound AR. The middle region of N-CoR mostly contributed to the interaction with agonist-bound SHRs and the suppression of their transactivation function. N-CoR impaired the DHT-induced N-C interaction of AR, and the impaired interaction was dose-dependently recovered by coexpression of SRC-1 and CBP. N-CoR also impaired the intranuclear complete (distinct) focus formation of SHRs. Coexpression of SRC-1 or CBP released YFP-N-CoR or endogenous N-CoR from incomplete foci and simultaneously recovered complete foci of AR-green fluorescent protein. These results indicate that the relative ratio of coactivators and corepressors determines the conformational equilibrium between transcriptionally active and inactive SHRs in the presence of agonists. The intranuclear foci formed by agonist-bound SHRs were completely destroyed by actinomycin D and α-amanitin, indicating that the focus formation does not precede the transcriptional activation. The focus formation may reflect the accumulation of SHR/coactivator complexes released from the transcriptionally active sites and thus be a mirror of transcriptionally active complex formation.

Original languageEnglish
Pages (from-to)6633-6655
Number of pages23
JournalMolecular and cellular biology
Volume26
Issue number17
DOIs
Publication statusPublished - Sep 2006

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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