PMID- 22446693
OWN - NLM
STAT- MEDLINE
DCOM- 20120905
LR  - 20231120
IS  - 1546-1696 (Electronic)
IS  - 1087-0156 (Print)
IS  - 1087-0156 (Linking)
VI  - 30
IP  - 5
DP  - 2012 Mar 25
TI  - Inhibition of natural antisense transcripts in vivo results in gene-specific 
      transcriptional upregulation.
PG  - 453-9
LID - 10.1038/nbt.2158 [doi]
AB  - The ability to specifically upregulate genes in vivo holds great therapeutic 
      promise. Here we show that inhibition or degradation of natural antisense 
      transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently 
      and reversibly upregulate locus-specific gene expression. Brain-derived 
      neurotrophic factor (BDNF) is normally repressed by a conserved noncoding 
      antisense RNA transcript, BDNF-AS. Inhibition of this transcript upregulates BDNF 
      mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to 
      increased protein levels and induces neuronal outgrowth and differentiation both 
      in vitro and in vivo. We also show that inhibition of NATs leads to increases in 
      glial-derived neurotrophic factor (GDNF) and ephrin receptor B2 (EPHB2) mRNA. Our 
      data suggest that pharmacological approaches targeting NATs can confer 
      locus-specific gene upregulation effects.
FAU - Modarresi, Farzaneh
AU  - Modarresi F
AD  - Department of Psychiatry and Behavioral Sciences and Center for Therapeutic 
      Innovation, John P. Hussman Institute for Human Genomics, University of Miami 
      Miller School of Medicine, Miami, Florida, USA.
FAU - Faghihi, Mohammad Ali
AU  - Faghihi MA
FAU - Lopez-Toledano, Miguel A
AU  - Lopez-Toledano MA
FAU - Fatemi, Roya Pedram
AU  - Fatemi RP
FAU - Magistri, Marco
AU  - Magistri M
FAU - Brothers, Shaun P
AU  - Brothers SP
FAU - van der Brug, Marcel P
AU  - van der Brug MP
FAU - Wahlestedt, Claes
AU  - Wahlestedt C
LA  - eng
GR  - R01 NS063974-05/NS/NINDS NIH HHS/United States
GR  - RC2 AG036596-01/AG/NIA NIH HHS/United States
GR  - R01 NS063974-01A1/NS/NINDS NIH HHS/United States
GR  - R01 NS063974/NS/NINDS NIH HHS/United States
GR  - 5R01NS063974/NS/NINDS NIH HHS/United States
GR  - RC2 AG036596-02/AG/NIA NIH HHS/United States
GR  - 5RC2AG036596/AG/NIA NIH HHS/United States
GR  - R01 NS063974-04/NS/NINDS NIH HHS/United States
GR  - RC2 AG036596/AG/NIA NIH HHS/United States
GR  - R01 NS063974-02/NS/NINDS NIH HHS/United States
GR  - RC2 AG036596-03/AG/NIA NIH HHS/United States
GR  - R01 NS063974-03/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120325
PL  - United States
TA  - Nat Biotechnol
JT  - Nature biotechnology
JID - 9604648
RN  - 0 (Chromatin)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.10.1 (Receptor, EphB2)
SB  - IM
CIN - Nat Methods. 2012 May;9(5):437. PMID: 22803202
MH  - Animals
MH  - Cell Line
MH  - Chromatin/chemistry/metabolism
MH  - Exons
MH  - Gene Expression Profiling
MH  - Genomics
MH  - Glial Cell Line-Derived Neurotrophic Factor/biosynthesis
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - Models, Genetic
MH  - Oligonucleotides, Antisense/*antagonists & inhibitors
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Receptor, EphB2/biosynthesis
MH  - Sequence Analysis, DNA
MH  - Transcription, Genetic
MH  - *Up-Regulation
PMC - PMC4144683
MID - NIHMS357438
EDAT- 2012/03/27 06:00
MHDA- 2012/09/06 06:00
PMCR- 2014/08/26
CRDT- 2012/03/27 06:00
PHST- 2011/09/29 00:00 [received]
PHST- 2012/02/14 00:00 [accepted]
PHST- 2012/03/27 06:00 [entrez]
PHST- 2012/03/27 06:00 [pubmed]
PHST- 2012/09/06 06:00 [medline]
PHST- 2014/08/26 00:00 [pmc-release]
AID - nbt.2158 [pii]
AID - 10.1038/nbt.2158 [doi]
PST - epublish
SO  - Nat Biotechnol. 2012 Mar 25;30(5):453-9. doi: 10.1038/nbt.2158.