PMID- 31181625
OWN - NLM
STAT- MEDLINE
DCOM- 20191118
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 11
DP  - 2019 Jun 7
TI  - Repression of TERRA Expression by Subtelomeric DNA Methylation Is Dependent on 
      NRF1 Binding.
LID - 10.3390/ijms20112791 [doi]
LID - 2791
AB  - Chromosome ends are transcribed into long noncoding telomeric repeat-containing 
      RNA (TERRA) from subtelomeric promoters. A class of TERRA promoters are 
      associated with CpG islands embedded in repetitive DNA tracts. Cytosines in these 
      subtelomeric CpG islands are frequently methylated in telomerase-positive cancer 
      cells, and demethylation induced by depletion of DNA methyltransferases is 
      associated with increased TERRA levels. However, the direct evidence and the 
      underlying mechanism regulating TERRA expression through subtelomeric CpG islands 
      methylation are still to establish. To analyze TERRA regulation by subtelomeric 
      DNA methylation in human cell line (HeLa), we used an epigenetic engineering tool 
      based on CRISPR-dCas9 (clustered regularly interspaced short palindromic repeats 
      - dead CRISPR associated protein 9) associated with TET1 (ten-eleven 1 
      hydroxylase) to specifically demethylate subtelomeric CpG islands. This targeted 
      demethylation caused an up-regulation of TERRA, and the enhanced TERRA production 
      depended on the methyl-sensitive transcription factor NRF1 (nuclear respiratory 
      factor 1). Since AMPK (AMP-activated protein kinase) is a well-known activator of 
      NRF1, we treated cells with an AMPK inhibitor (compound C). Surprisingly, 
      compound C treatment increased TERRA levels but did not inhibit AMPK activity in 
      these experimental conditions. Altogether, our results provide new insight in the 
      fine-tuning of TERRA at specific subtelomeric promoters and could allow 
      identifying new regulators of TERRA.
FAU - Le Berre, Gabriel
AU  - Le Berre G
AD  - Structure et Instabilite des Genomes, Museum National d'Histoire Naturelle, CNRS 
      UMR 7196, INSERM U1154, 43 rue Cuvier, F-75005 Paris, France. 
      gabriel.le-berre@mnhn.fr.
FAU - Hossard, Virginie
AU  - Hossard V
AD  - Structure et Instabilite des Genomes, Museum National d'Histoire Naturelle, CNRS 
      UMR 7196, INSERM U1154, 43 rue Cuvier, F-75005 Paris, France. 
      virginie.hossard@mnhn.fr.
FAU - Riou, Jean-Francois
AU  - Riou JF
AD  - Structure et Instabilite des Genomes, Museum National d'Histoire Naturelle, CNRS 
      UMR 7196, INSERM U1154, 43 rue Cuvier, F-75005 Paris, France. 
      jean-francois.riou@mnhn.fr.
FAU - Guieysse-Peugeot, Anne-Laure
AU  - Guieysse-Peugeot AL
AD  - Structure et Instabilite des Genomes, Museum National d'Histoire Naturelle, CNRS 
      UMR 7196, INSERM U1154, 43 rue Cuvier, F-75005 Paris, France. guieysse@mnhn.fr.
LA  - eng
PT  - Journal Article
DEP - 20190607
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (NRF1 protein, human)
RN  - 0 (Nuclear Respiratory Factor 1)
RN  - 0 (RNA, Long Noncoding)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - CpG Islands
MH  - *DNA Methylation
MH  - Epigenesis, Genetic
MH  - HeLa Cells
MH  - Humans
MH  - Nuclear Respiratory Factor 1/*metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Kinases/metabolism
MH  - RNA, Long Noncoding/genetics/metabolism
MH  - Repetitive Sequences, Nucleic Acid/genetics
MH  - Telomere/*genetics/metabolism
PMC - PMC6600276
OTO - NOTNLM
OT  - DNA methylation
OT  - NRF1
OT  - TERRA
OT  - epigenetic regulation
OT  - targeted demethylation
OT  - telomeres
COIS- The authors declare no conflict of interest.
EDAT- 2019/06/12 06:00
MHDA- 2019/11/19 06:00
PMCR- 2019/06/01
CRDT- 2019/06/12 06:00
PHST- 2019/04/27 00:00 [received]
PHST- 2019/05/29 00:00 [revised]
PHST- 2019/06/04 00:00 [accepted]
PHST- 2019/06/12 06:00 [entrez]
PHST- 2019/06/12 06:00 [pubmed]
PHST- 2019/11/19 06:00 [medline]
PHST- 2019/06/01 00:00 [pmc-release]
AID - ijms20112791 [pii]
AID - ijms-20-02791 [pii]
AID - 10.3390/ijms20112791 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Jun 7;20(11):2791. doi: 10.3390/ijms20112791.