Linked Life Data

20135341

Source:http://linkedlifedata.com/resource/pubmed/id/20135341

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7-8
pubmed:dateCreated
2010-3-16
pubmed:abstractText
Adult skeletal muscles retain an adaptive capacity to switch between slow- and fast-twitch properties that are largely dependent on motoneuron activity. Our studies on the transcriptional regulation of the Troponin I slow (TnIs) and fast (TnIf) genes uncovered a dual mechanism of transcriptional enhancement and repression by a single activity pattern, that promotes the phenotypic differences among myofibers while preserving their adaptive capacity. Using the Tnf Fast Intronic Regulatory Element (FIRE), we initially demonstrated that fast-patterned activity (infrequent, high frequency depolarization) is necessary to up-regulate FIRE-dependent transcription and that its effect differs dramatically from muscle denervation. Hence, the "fast muscle program" is not a default state mimicked simply by denervation or muscle inactivity. Next, we found that slow-patterned activity (tonic, slow frequency stimulation) selectively represses FIRE-dependent transcription while enhancing transcription from the TnIs Slow Upstream Regulatory Element. Unexpectedly, repression of the TnIf FIRE by slow-patterned activity is mediated by an NFAT element that directly binds NFATc1, a transcription factor that translocates to the nucleus selectively by slow-pattern depolarization and has been implicated in the up-regulation of the slow muscle program. Transfection of siRNAs targeting NFATc1 or mutation of the TnIFIRE NFAT site result in the upregulation of FIRE-dependent transcription in slow muscle, but have no effect in fast muscle. These findings demonstrate a novel function of NFAT as a repressor of transcription of fast contractile genes in slow muscles and, more importantly, they illustrate how specific activity patterns can enhance the phenotypic differences among fibre-types by differentially regulating transcription in a use-dependent manner while retaining the adaptive properties of adult muscles.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1573-2657
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
255-60
pubmed:dateRevised
2010-9-24
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The ups and downs of gene regulation by electrical activity in skeletal muscles.
pubmed:affiliation
Department of Molecular Biosciences, University of Oslo, Oslo, Norway. z.a.rana@imbv.uio.no
pubmed:publicationType
Journal Article, Review