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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
1998-9-10
pubmed:abstractText
The sodium/myo-inositol cotransporter is a plasma membrane protein responsible for concentrative cellular accumulation of myo-inositol in a variety of tissues. When cells in kidney and brain are exposed to a hyperosmolar salt condition (hypertonicity) due to the operation of urinary concentration mechanism and pathological conditions, respectively, they survive the stress of hypertonicity by raising the cellular concentration of myo-inositol. Transcription of the sodium/myo-inositol cotransporter gene is markedly stimulated in response to hypertonicity, leading to an increase in the activity of the cotransporter, which in turn drives the osmoprotective accumulation of myo-inositol. To understand the molecular mechanisms by which hypertonicity stimulates transcription, we analyzed the 5'-flanking region of the cotransporter gene for cis-acting regulatory sequences. We identified five tonicity-responsive enhancers that are scattered over 50 kilobase pairs. All the enhancers are variations of the same type of enhancer interacting with the transcription factor named tonicity-responsive enhancer binding protein. In vivo methylation experiments demonstrated that exposure of cells to hypertonicity increases the binding of tonicity-responsive enhancer binding protein to the enhancer sites, indicating that all of these enhancers are involved in the transcriptional stimulation. We conclude that the sodium/myo-inositol cotransporter gene is regulated by a large region (approximately 50 kilobase pairs) upstream of the gene.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-1372904, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-1550215, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-1864974, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-1924548, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-2493741, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-7112124, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-7495565, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-7537337, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-7544754, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-7657791, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-7675106, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-7948784, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-7961914, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-8120010, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-8196651, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-8430828, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-8473504, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-8476251, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-8717373, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-8779931, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-8840014, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-8898018, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-9124406, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-9143369, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-9195951, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-9299172, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-9441750, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-9453011, http://linkedlifedata.com/resource/pubmed/commentcorrection/9685419-9575900
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20615-21
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:9685419-Animals, pubmed-meshheading:9685419-Base Sequence, pubmed-meshheading:9685419-Biological Transport, pubmed-meshheading:9685419-Carrier Proteins, pubmed-meshheading:9685419-Cell Line, pubmed-meshheading:9685419-Cell Membrane, pubmed-meshheading:9685419-Cloning, Molecular, pubmed-meshheading:9685419-DNA-Binding Proteins, pubmed-meshheading:9685419-Enhancer Elements, Genetic, pubmed-meshheading:9685419-Gene Expression Regulation, pubmed-meshheading:9685419-Genes, Reporter, pubmed-meshheading:9685419-Heat-Shock Proteins, pubmed-meshheading:9685419-Hypertonic Solutions, pubmed-meshheading:9685419-Inositol, pubmed-meshheading:9685419-Membrane Proteins, pubmed-meshheading:9685419-Molecular Sequence Data, pubmed-meshheading:9685419-Osmolar Concentration, pubmed-meshheading:9685419-Symporters, pubmed-meshheading:9685419-Transcription, Genetic, pubmed-meshheading:9685419-Transcription Factors, pubmed-meshheading:9685419-Transfection
pubmed:year
1998
pubmed:articleTitle
Transcription of the sodium/myo-inositol cotransporter gene is regulated by multiple tonicity-responsive enhancers spread over 50 kilobase pairs in the 5'-flanking region.
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