rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2006-6-9
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pubmed:abstractText |
INSM1/IA-1 (insulinoma-associated 1) is a developmentally regulated zinc-finger transcription factor, exclusively expressed in the foetal pancreas and nervous system, and in tumours of neuroendocrine origin. We have identified an INSM1 binding site in the neuroD/beta2 promoter and demonstrated transcriptional repressor activity of INSM1 by transient transfection assay. A chromatin immunoprecipitation assay confirmed that in vivo INSM1 is situated on the promoter region of the neuroD/beta2 gene. In an attempt to elucidate the molecular mechanism of transcriptional repression by the INSM1 gene, cyclin D1 was identified as an interacting protein by using a 45-day-old human foetal brain cDNA library and a yeast two-hybrid screen. The physical association between INSM1 and cyclin D1 was confirmed by in vitro and in vivo pull-down assay. Cyclin D1 co-operates with INSM1 and suppresses neuroD/beta2 promoter activity. Co-immunoprecipitation of INSM1, cyclin D1 and HDACs (histone deacetylases) in mammalian cells revealed that INSM1 interacts with HDAC-1 and -3 and that this interaction is mediated through cyclin D1. Overexpression of cyclin D1 and HDAC-3 significantly enhanced the transcriptional repression activity of INSM1 on the neuroD/beta2 promoter. A further chromatin immunoprecipitation assay confirmed that HDAC-3 occupies this same region of the neuroD/beta2 promoter, by forming a transcription complex with INSM1. Thus we conclude that INSM1 recruits cyclin D1 and HDACs, which confer transcriptional repressor activity.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16569215-10022835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16569215-10064602,
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HDAC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/INSM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NEUROD1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1470-8728
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
397
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
169-77
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16569215-Adenoviridae,
pubmed-meshheading:16569215-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:16569215-Brain Stem Neoplasms,
pubmed-meshheading:16569215-Chromatin Immunoprecipitation,
pubmed-meshheading:16569215-Cyclin D1,
pubmed-meshheading:16569215-DNA-Binding Proteins,
pubmed-meshheading:16569215-Histone Deacetylase 1,
pubmed-meshheading:16569215-Histone Deacetylase 2,
pubmed-meshheading:16569215-Histone Deacetylases,
pubmed-meshheading:16569215-Humans,
pubmed-meshheading:16569215-Kidney,
pubmed-meshheading:16569215-Medulloblastoma,
pubmed-meshheading:16569215-Plasmids,
pubmed-meshheading:16569215-Promoter Regions, Genetic,
pubmed-meshheading:16569215-Repressor Proteins,
pubmed-meshheading:16569215-Transcription, Genetic,
pubmed-meshheading:16569215-Tumor Cells, Cultured,
pubmed-meshheading:16569215-Two-Hybrid System Techniques
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pubmed:year |
2006
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pubmed:articleTitle |
INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of cyclin D1 and histone deacetylases.
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pubmed:affiliation |
The Research Institute for Children, Children's Hospital, New Orleans, LA 70118, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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