LncRNA Khps1 Regulates Expression of the Proto-oncogene SPHK1 via Triplex-Mediated Changes in Chromatin Structure

Anna Postepska-Igielska, Alena Giwojna, Lital Gasri-Plotnitsky, Nina Schmitt, Annabelle Dold, Doron Ginsberg, Ingrid Grummt

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Although thousands of long noncoding RNAs (lncRNAs) have been discovered, very little is known about their mode of action. Here we functionally characterize an E2F1-regulated lncRNA named Khps1, which is transcribed in antisense orientation to the proto-oncogene SPHK1. Khps1 activates SPHK1 expression by recruiting the histone acetyltransferase p300/CBP to the SPHK1 promoter, which leads to local changes of the chromatin structure that ensures E2F1 binding and enhances transcription. Mechanistically, this is achieved by direct association of Khps1 with a homopurine stretch upstream of the transcription start site of SPHK1, which forms a DNA-RNA triplex that anchors the lncRNA and associated effector proteins to the gene promoter. The results reveal an lncRNA- and E2F1-driven regulatory loop in which E2F1-dependent induction of antisense RNA leads to changes in chromatin structure, facilitating E2F1-dependent expression of SPHK1 and restriction of E2F1-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)626-636
Number of pages11
JournalMolecular cell
Volume60
Issue number4
DOIs
StatePublished - Nov 19 2015

Fingerprint

Long Noncoding RNA
Proto-Oncogenes
Chromatin
Histone Acetyltransferases
Antisense RNA
Transcription Initiation Site
RNA
Apoptosis
Proteins

Keywords

  • Antisense
  • Chromatin
  • E2F1
  • Khps1
  • LncRNA
  • P300
  • SPHK1
  • Triplex

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

LncRNA Khps1 Regulates Expression of the Proto-oncogene SPHK1 via Triplex-Mediated Changes in Chromatin Structure. / Postepska-Igielska, Anna; Giwojna, Alena; Gasri-Plotnitsky, Lital; Schmitt, Nina; Dold, Annabelle; Ginsberg, Doron; Grummt, Ingrid.

In: Molecular cell, Vol. 60, No. 4, 19.11.2015, p. 626-636.

Research output: Contribution to journalArticle

Postepska-Igielska, A, Giwojna, A, Gasri-Plotnitsky, L, Schmitt, N, Dold, A, Ginsberg, D & Grummt, I 2015, 'LncRNA Khps1 Regulates Expression of the Proto-oncogene SPHK1 via Triplex-Mediated Changes in Chromatin Structure', Molecular cell, vol. 60, no. 4, pp. 626-636. https://doi.org/10.1016/j.molcel.2015.10.001
Postepska-Igielska A, Giwojna A, Gasri-Plotnitsky L, Schmitt N, Dold A, Ginsberg D et al. LncRNA Khps1 Regulates Expression of the Proto-oncogene SPHK1 via Triplex-Mediated Changes in Chromatin Structure. Molecular cell. 2015 Nov 19;60(4):626-636. https://doi.org/10.1016/j.molcel.2015.10.001
Postepska-Igielska, Anna ; Giwojna, Alena ; Gasri-Plotnitsky, Lital ; Schmitt, Nina ; Dold, Annabelle ; Ginsberg, Doron ; Grummt, Ingrid. / LncRNA Khps1 Regulates Expression of the Proto-oncogene SPHK1 via Triplex-Mediated Changes in Chromatin Structure. In: Molecular cell. 2015 ; Vol. 60, No. 4. pp. 626-636.
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