lncRNA KHPS1 Activates a Poised Enhancer by Triplex-Dependent Recruitment of Epigenomic Regulators.
CTCF
E2F1
RNA-DNA triplexes
SPHK1
eRNA
lncRNA
p300
poised enhancer
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
12 03 2019
12 03 2019
Historique:
received:
08
05
2018
revised:
14
11
2018
accepted:
14
02
2019
entrez:
14
3
2019
pubmed:
14
3
2019
medline:
16
4
2020
Statut:
ppublish
Résumé
Transcription of the proto-oncogene SPHK1 is regulated by KHPS1, an antisense RNA that activates SPHK1 expression by forming a triple-helical RNA-DNA-DNA structure at the SPHK1 enhancer. Triplex-mediated tethering of KHPS1 to its target gene is required for recruitment of E2F1 and p300 and transcription of the RNA derived from the SPHK1 enhancer (eRNA-Sphk1). eRNA-Sphk1 evicts CTCF, which insulates the enhancer from the SPHK1 promoter, thus facilitating SPHK1 expression. Genomic deletion of the triplex-forming sequence attenuates SPHK1 expression, leading to decreased cell migration and invasion. Replacement of the triplex-forming region (TFR) of KHPS1 by the TFR of the lncRNA MEG3 tethers KHPS1 to the MEG3 target gene TGFBR1, underscoring the interchangeability and anchoring function of sequences involved in triplex formation. Altogether, the results reveal a triplex-driven feedforward mechanism involving lncRNA-dependent induction of eRNA, which enhances expression of specific target genes.
Identifiants
pubmed: 30865882
pii: S2211-1247(19)30238-4
doi: 10.1016/j.celrep.2019.02.059
pii:
doi:
Substances chimiques
Khps1 long noncoding RNA, human
0
MAS1 protein, human
0
MEG3 non-coding RNA, human
0
Proto-Oncogene Mas
0
RNA, Long Noncoding
0
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
sphingosine kinase
EC 2.7.1.-
Receptor, Transforming Growth Factor-beta Type I
EC 2.7.11.30
TGFBR1 protein, human
EC 2.7.11.30
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2904-2915.e4Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.