PMID- 11238943
OWN - NLM
STAT- MEDLINE
DCOM- 20010419
LR  - 20181113
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 21
IP  - 6
DP  - 2001 Mar
TI  - The neuron-restrictive silencer element-neuron-restrictive silencer factor system 
      regulates basal and endothelin 1-inducible atrial natriuretic peptide gene 
      expression in ventricular myocytes.
PG  - 2085-97
AB  - Induction of the atrial natriuretic peptide (ANP) gene is a common feature of 
      ventricular hypertrophy. A number of cis-acting enhancer elements for several 
      transcriptional activators have been shown to play central roles in the 
      regulation of ANP gene expression, but much less is known about contributions 
      made by transcriptional repressors. The neuron-restrictive silencer element 
      (NRSE), also known as repressor element 1, mediates repression of neuronal gene 
      expression in nonneuronal cells. We found that NRSE, which is located in the 3' 
      untranslated region of the ANP gene, mediated repression of ANP promoter activity 
      in ventricular myocytes and was also involved in the endothelin 1-induced 
      increase in ANP gene transcription. The repression was conferred by a repressor 
      protein, neuron-restrictive silencer factor (NRSF). NRSF associated with the 
      transcriptional corepressor mSin3 and formed a complex with histone deacetylase 
      (HDAC) in ventricular myocytes. Trichostatin A (TSA), a specific HDAC inhibitor, 
      relieved NRSE-mediated repression of ANP promoter activity, and chromatin 
      immunoprecipitation assays revealed the involvement of histone deacetylation in 
      NRSE-mediated repression of ANP gene expression. Furthermore, in myocytes 
      infected with recombinant adenovirus expressing a dominant-negative form of NRSF, 
      the basal level of endogenous ANP gene expression was increased and a TSA-induced 
      increase in ANP gene expression was apparently attenuated, compared with those in 
      myocytes infected with control adenovirus. Our findings show that an NRSE-NRSF 
      system plays a key role in the regulation of ANP gene expression by HDAC in 
      ventricular myocytes and provide a new insight into the role of the NRSE-NRSF 
      system outside the nervous system.
FAU - Kuwahara, K
AU  - Kuwahara K
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto 606-8397, Japan.
FAU - Saito, Y
AU  - Saito Y
FAU - Ogawa, E
AU  - Ogawa E
FAU - Takahashi, N
AU  - Takahashi N
FAU - Nakagawa, Y
AU  - Nakagawa Y
FAU - Naruse, Y
AU  - Naruse Y
FAU - Harada, M
AU  - Harada M
FAU - Hamanaka, I
AU  - Hamanaka I
FAU - Izumi, T
AU  - Izumi T
FAU - Miyamoto, Y
AU  - Miyamoto Y
FAU - Kishimoto, I
AU  - Kishimoto I
FAU - Kawakami, R
AU  - Kawakami R
FAU - Nakanishi, M
AU  - Nakanishi M
FAU - Mori, N
AU  - Mori N
FAU - Nakao, K
AU  - Nakao K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Endothelin-1)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histones)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Repressor Proteins)
RN  - 0 (SIN3 protein, S cerevisiae)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Transcription Factors)
RN  - 3X2S926L3Z (trichostatin A)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Animals
MH  - Atrial Natriuretic Factor/*genetics
MH  - Cells, Cultured
MH  - Endothelin-1/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation, Developmental
MH  - Heart Ventricles/cytology/drug effects
MH  - Histone Deacetylase Inhibitors
MH  - Histone Deacetylases/metabolism
MH  - Histones/metabolism
MH  - Hydroxamic Acids/pharmacology
MH  - Mutation
MH  - Neurons/*physiology
MH  - Organ Specificity
MH  - Rats
MH  - *Regulatory Sequences, Nucleic Acid
MH  - *Repressor Proteins
MH  - *Saccharomyces cerevisiae Proteins
MH  - Transcription Factors
MH  - Transcription, Genetic
MH  - *Ventricular Function
PMC - PMC86819
EDAT- 2001/03/10 10:00
MHDA- 2001/04/21 10:01
PMCR- 2001/03/01
CRDT- 2001/03/10 10:00
PHST- 2001/03/10 10:00 [pubmed]
PHST- 2001/04/21 10:01 [medline]
PHST- 2001/03/10 10:00 [entrez]
PHST- 2001/03/01 00:00 [pmc-release]
AID - 1772 [pii]
AID - 10.1128/MCB.21.6.2085-2097.2001 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2001 Mar;21(6):2085-97. doi: 10.1128/MCB.21.6.2085-2097.2001.