PMID- 26595656
OWN - NLM
STAT- MEDLINE
DCOM- 20160526
LR  - 20181113
IS  - 1546-1726 (Electronic)
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 19
IP  - 1
DP  - 2016 Jan
TI  - Stimulus-specific combinatorial functionality of neuronal c-fos enhancers.
PG  - 75-83
LID - 10.1038/nn.4170 [doi]
AB  - The c-fos gene (also known as Fos) is induced by a broad range of stimuli and is 
      a reliable marker for neural activity. Its induction mechanism and available 
      reporter mouse lines are based exclusively on c-fos promoter activity. Here we 
      demonstrate that multiple enhancers surrounding the c-fos gene are crucial for 
      ensuring robust c-fos response to various stimuli. Membrane depolarization, 
      brain-derived neurotrophic factor (BDNF) and forskolin activate distinct subsets 
      of the enhancers to induce c-fos transcription in neurons, suggesting that 
      stimulus-specific combinatorial activation of multiple enhancers underlies the 
      broad inducibility of the c-fos gene. Accordingly, the functional requirement of 
      key transcription factors varies depending on the type of stimulation. 
      Combinatorial enhancer activation also occurs in the brain. Providing a 
      comprehensive picture of the c-fos induction mechanism beyond the minimal 
      promoter, our study should help in understanding the physiological nature of 
      c-fos induction in relation to neural activity and plasticity.
FAU - Joo, Jae-Yeol
AU  - Joo JY
AD  - Department of Neuroscience, The University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
FAU - Schaukowitch, Katie
AU  - Schaukowitch K
AD  - Department of Neuroscience, The University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
FAU - Farbiak, Lukas
AU  - Farbiak L
AD  - Department of Neuroscience, The University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
FAU - Kilaru, Gokhul
AU  - Kilaru G
AD  - Department of Neuroscience, The University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
FAU - Kim, Tae-Kyung
AU  - Kim TK
AD  - Department of Neuroscience, The University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
LA  - eng
GR  - R01 NS085418/NS/NINDS NIH HHS/United States
GR  - R01NS085418/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20151123
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
SB  - IM
EIN - Nat Neurosci. 2016 Apr;19(4):642. PMID: 27021946
MH  - Animals
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Embryo, Mammalian
MH  - *Enhancer Elements, Genetic
MH  - Epigenesis, Genetic
MH  - *Gene Expression
MH  - Genes, fos/*physiology
MH  - Mice
MH  - Neuronal Plasticity
MH  - Neurons/*metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger
MH  - *Transcription, Genetic
PMC - PMC4696896
MID - NIHMS731484
COIS- COMPETING FINANCIAL INTERESTS The authors declare no competing financial 
      interests.
EDAT- 2015/11/26 06:00
MHDA- 2016/05/27 06:00
PMCR- 2016/05/23
CRDT- 2015/11/24 06:00
PHST- 2015/08/11 00:00 [received]
PHST- 2015/10/09 00:00 [accepted]
PHST- 2015/11/24 06:00 [entrez]
PHST- 2015/11/26 06:00 [pubmed]
PHST- 2016/05/27 06:00 [medline]
PHST- 2016/05/23 00:00 [pmc-release]
AID - nn.4170 [pii]
AID - 10.1038/nn.4170 [doi]
PST - ppublish
SO  - Nat Neurosci. 2016 Jan;19(1):75-83. doi: 10.1038/nn.4170. Epub 2015 Nov 23.