Identification of estrogen receptor-related receptor gamma as a direct transcriptional target of angiogenin

PLoS One. 2013 Aug 15;8(8):e71487. doi: 10.1371/journal.pone.0071487. eCollection 2013.

Abstract

Nuclear translocation of angiogenin (ANG) is essential for the proliferation of its target cells. ANG promotes rRNA synthesis, while whether it regulates mRNA transcription remains unknown. Using the chromatin immunoprecipitation method, we have identified 12 ANG-binding sequences. One of these sequences lies in the estrogen receptor-related receptor gamma (ERRγ) gene which we designated as ANG-Binding Sequence within ERRγ (ABSE). ABSE exhibited ANG-dependent repressor activity in the luciferase reporter system. Down-regulation of ANG increased ERRγ expression, and active gene marker level at the ABSE region. The expression levels of ERRγ targets genes, p21(WAF/CIP) and p27(KIP1), and the occupation of ERRγ on their promoter regions were increased in ANG-deficient cells accordingly. Furthermore, knockdown of ERRγ promoted the proliferation rate in ANG-deficient breast cancer cells. Finally, immunohistochemistry staining showed negative correlation between ANG and ERRγ in breast cancer tissue. Altogether, our study provides evidence that nuclear ANG directly binds to the ABSE of ERRγ gene and inhibits ERRγ transcription to promote breast cancer cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histones / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Protein Binding / genetics
  • Protein Processing, Post-Translational
  • RNA Polymerase II / metabolism
  • Receptors, Estrogen / metabolism*
  • Ribonuclease, Pancreatic / metabolism*
  • Transcription, Genetic*

Substances

  • ESRRG protein, human
  • Histones
  • Receptors, Estrogen
  • RNA Polymerase II
  • angiogenin
  • Ribonuclease, Pancreatic

Grants and funding

This work was supported by the grants from National Natural Science Foundation of China (No. 30770470, 30900235, and 31170721). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.