Author/Editor     Chen-Plotkin, Alice S; Sadri-Vakili, Ghazaleh; Yohrling, George J; Braveman, Melissa W; Benn, Caroline L; Glajch, Kelly E; DiRocco, Derek P; Farrell, Laurie A; Krainc, Dimitri; Gines, Silvia
Title     Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease
Type     članek
Source     Neurobiol Dis
Vol. and No.     Letnik 22, št. 2
Publication year     2006
Volume     str. 233-41
Language     eng
Abstract     Huntington's disease (HD) is a neurodegenerative disease caused by expansion of a polyglutamine tract within the huntingtin protein. Transcriptional dysregulation has been implicated in HD pathogenesis; recent evidence suggests a defect in Sp1-mediated transcription. We used chromatin immunoprecipitation (ChIP) assays followed by real-time PCR to quantify the association of Sp1 with individual genes. We find that, despite normal protein levels and normal to increased overall nuclear binding activity, Sp1 has decreased binding to specific promoters of susceptible genes in transgenic HD mouse brain, in striatal HD cells, and in human HD brain. Genes whose mRNA levels are decreased in HD have abnormal Sp1-DNA binding, whereas genes with unchanged mRNA levels have normal levels of Sp1 association. Moreover, the altered binding seen with Sp1 is not found with another transcription factor, NF-Y. These findings suggest that mutant huntingtin dissociates Sp1 from target promoters, inhibiting transcription of specific genes.
Descriptors     ANIMALS
BINDING SITES
BRAIN
BRAIN CHEMISTRY
CELLS, CULTURED
GENE EXPRESSION REGULATION
MICE
MICE, TRANSGENIC
NERVE TISSUE PROTEINS
NUCLEAR PROTEINS
PROTEIN BINDING