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Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor
- Source :
- The EMBO Journal. 27:827-839
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- In Huntington's disease (HD), mutant Huntingtin, which contains expanded polyglutamine stretches, forms nuclear aggregates in neurons. The interactions of several transcriptional factors with mutant Huntingtin, as well as altered expression of many genes in HD models, imply the involvement of transcriptional dysregulation in the HD pathological process. The precise mechanism remains obscure, however. Here, we show that mutant Huntingtin aggregates interact with the components of the NF-Y transcriptional factor in vitro and in HD model mouse brain. An electrophoretic mobility shift assay using HD model mouse brain lysates showed reduction in NF-Y binding to the promoter region of HSP70, one of the NF-Y targets. RT–PCR analysis revealed reduced HSP70 expression in these brains. We further clarified the importance of NF-Y for HSP70 transcription in cultured neurons. These data indicate that mutant Huntingtin sequesters NF-Y, leading to the reduction of HSP70 gene expression in HD model mice brain. Because suppressive roles of HSP70 on the HD pathological process have been shown in several HD models, NF-Y could be an important target of mutant Huntingtin.
- Subjects :
- Male
Huntingtin
Mutant
Mice, Transgenic
Nerve Tissue Proteins
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Mice
Huntington's disease
Transcription (biology)
Cell Line, Tumor
medicine
Huntingtin Protein
Animals
HSP70 Heat-Shock Proteins
Electrophoretic mobility shift assay
Molecular Biology
Transcription factor
General Immunology and Microbiology
General Neuroscience
Nuclear Proteins
Promoter
medicine.disease
Molecular biology
Disease Models, Animal
Huntington Disease
CCAAT-Binding Factor
nervous system
Mutation
Protein Binding
Subjects
Details
- ISSN :
- 14602075 and 02614189
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- The EMBO Journal
- Accession number :
- edsair.doi.dedup.....2cbbc8af217e21cb97e232aea7a6f979