UHRF1 regulates CDH1 via promoter associated non-coding RNAs in prostate cancer cells

Biochim Biophys Acta Gene Regul Mech. 2018 Mar;1861(3):258-270. doi: 10.1016/j.bbagrm.2018.02.006. Epub 2018 Feb 18.


Non-coding RNAs (ncRNAs) transcribed from the promoter and the downstream region can affect the expression of the corresponding coding genes. It has been shown that sense-directed ncRNAs arising from the promoter region of the E-cadherin gene (CDH1) mediate its repression. Here, we show that an antisense-directed ncRNA (paRCDH1-AS) transcribed from the CDH1 promoter is necessary for its expression. paRCDH1-AS acts as a hooking scaffold by recruiting the epigenetic regulators, UHRF1, DNMT3A, SUV39H1 and SUZ12, involved in CDH1 repression. The binding of epigenetic regulators to paCRDH1-AS, indeed, prevents their localization to the chromatin on CDH1 promoter. Moreover, paRCDH1-AS silencing induces CDH1 repression and a switch of the epigenetic profile on the promoter towards a more closed chromatin. Using bioinformatic and experimental approaches we defined that the promoter of the paRCDH1-AS is shared with the E-cadherin gene, showing a bidirectional promoter activity. We found that UHRF1 controls both CDH1 and paRCDH1-AS by directly binding this bidirectional promoter region. Our study provides evidences, for the first time, that UHRF1 recruitment can be affected by promoter-associated non-coding RNAs, opening new perspective regarding the role of UHRF1 in these complex regulatory networks.

Keywords: Bidirectional promoters; CDH1; Promoter-associated non-coding RNAs; UHRF1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Male
  • Models, Biological
  • Promoter Regions, Genetic*
  • Prostatic Neoplasms / genetics*
  • Protein Binding / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • Ubiquitin-Protein Ligases


  • Antigens, CD
  • CCAAT-Enhancer-Binding Proteins
  • CDH1 protein, human
  • Cadherins
  • RNA, Messenger
  • RNA, Untranslated
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases