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PredicateObject
rdf:type
lifeskim:mentions
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.
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, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-12193541, 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, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-15086342, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-15820306, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-16236718, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-16315372, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-16782821, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-17289845, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-18045867, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-18160704, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-19036875, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-1961845, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-2253032, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-2319308, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-446419, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-6194291, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-8146169, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-8175765, http://linkedlifedata.com/resource/pubmed/commentcorrection/19359381-8491157, 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
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
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