Avtor/Urednik		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
Naslov		Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease
Tip		članek
Vir		Neurobiol Dis
Vol. in št.		Letnik 22, št. 2
Leto izdaje		2006
Obseg		str. 233-41
Jezik		eng
Abstrakt		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.
Deskriptorji		ANIMALS BINDING SITES BRAIN BRAIN CHEMISTRY CELLS, CULTURED GENE EXPRESSION REGULATION MICE MICE, TRANSGENIC NERVE TISSUE PROTEINS NUCLEAR PROTEINS PROTEIN BINDING