rdf:type |
|
lifeskim:mentions |
umls-concept:C0006104,
umls-concept:C0017262,
umls-concept:C0017337,
umls-concept:C0020792,
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0040135,
umls-concept:C0185117,
umls-concept:C0443281,
umls-concept:C0598509,
umls-concept:C1537487,
umls-concept:C2911684
|
pubmed:issue |
8
|
pubmed:dateCreated |
2009-7-22
|
pubmed:abstractText |
Brain development is critically dependent on thyroid hormone (T(3)). Krüppel-like factor 9 (Klf9) is a T(3)-inducible gene in developing rat brain, and several lines of evidence support that KLF9 plays a key role in neuronal morphogenesis. Here we extend our findings to the mouse and demonstrate the presence of a functional T(3) response element (T(3)RE) in the 5' flanking region of the mouse Klf9 gene. Klf9 mRNA is strongly induced in the mouse hippocampus and cerebellum in a developmental stage- and T(3)-dependent manner. Computer analysis identified a near optimal direct repeat 4 (DR-4) T(3)RE 3.8 kb upstream of the Klf9 transcription start site, and EMSAs showed that T(3) receptor (TR)-retinoid X receptor heterodimers bound to the T(3)RE with high affinity. The T(3)RE acts as a strong positive response element in transfection assays using a minimal heterologous promoter. In the mouse neuroblastoma cell line N2a[TRbeta1], T(3) caused a dose-dependent up-regulation of Klf9 mRNA. Chromatin immunoprecipitation assays conducted with N2a[TRbeta1] cells showed that TRs associated with the Klf9 T(3)RE, and this association was promoted by T(3). Treatment of N2a[TRbeta1] cells with T(3) led to hyperacetylation of histones 3 and 4 at the T(3)RE site. Furthermore, TRs associated with the DR-4 T(3)RE in postnatal d 4 mouse brain, and histone 4 acetylation was greater at this site compared with other regions of the Klf9 gene. Our study identifies a functional DR-4 T(3)RE located in the mouse Klf9 gene to explain its regulation by T(3) during mammalian brain development.
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pubmed:grant |
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-10438482,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-10876107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-11078533,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-11427693,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-11641275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-11847087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-11909518,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-11936472,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-12021188,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-12392570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-12446772,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-12620113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-12640131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-12824386,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-1356762,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-8521507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-8700860,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-9079635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-9238010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-9886843
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pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
AIM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Aug
|
pubmed:issn |
1945-7170
|
pubmed:author |
|
pubmed:issnType |
Electronic
|
pubmed:volume |
150
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
3935-43
|
pubmed:dateRevised |
2010-9-27
|
pubmed:meshHeading |
pubmed-meshheading:19359381-Acetylation,
pubmed-meshheading:19359381-Animals,
pubmed-meshheading:19359381-Animals, Newborn,
pubmed-meshheading:19359381-Brain,
pubmed-meshheading:19359381-Cell Line, Tumor,
pubmed-meshheading:19359381-Cerebellum,
pubmed-meshheading:19359381-Chromatin Immunoprecipitation,
pubmed-meshheading:19359381-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:19359381-Gene Expression Regulation,
pubmed-meshheading:19359381-Hippocampus,
pubmed-meshheading:19359381-Histones,
pubmed-meshheading:19359381-Kruppel-Like Transcription Factors,
pubmed-meshheading:19359381-Mice,
pubmed-meshheading:19359381-Mice, Inbred C57BL,
pubmed-meshheading:19359381-Response Elements,
pubmed-meshheading:19359381-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19359381-Thyroid Hormones,
pubmed-meshheading:19359381-Transcription Initiation Site,
pubmed-meshheading:19359381-Transfection,
pubmed-meshheading:19359381-Triiodothyronine
|
pubmed:year |
2009
|
pubmed:articleTitle |
Identification of a thyroid hormone response element in the mouse Kruppel-like factor 9 gene to explain its postnatal expression in the brain.
|
pubmed:affiliation |
Department of Molecular, Cellular, and Developmental Biology, The University of Michigan, Ann Arbor, Michigan 48109-1048, USA. rdenver@umich.edu
|
pubmed:publicationType |
Journal Article,
In Vitro
|