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Mol Cell. 2015 Nov 19;60(4):626-36. doi: 10.1016/j.molcel.2015.10.001.

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

Author information

1
Division of Molecular Biology of the Cell II, German Cancer Research Center, 69120 Heidelberg, Germany.
2
The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan 5299, Israel.
3
Division of Molecular Biology of the Cell II, German Cancer Research Center, 69120 Heidelberg, Germany. Electronic address: i.grummt@dkfz.de.

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.

KEYWORDS:

E2F1; Khps1; SPHK1; antisense; chromatin; lncRNA; p300; triplex

PMID:
26590717
DOI:
10.1016/j.molcel.2015.10.001
[Indexed for MEDLINE]
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