@article {2412,
	title = {In vitro analysis of huntingtin-mediated transcriptional repression reveals multiple transcription factor targets.},
	journal = {Cell},
	volume = {123},
	year = {2005},
	month = {2005 Dec 29},
	pages = {1241-53},
	abstract = {<p>Transcriptional dysregulation has emerged as a potentially important pathogenic mechanism in Huntington{\textquoteright}s disease, a neurodegenerative disorder associated with polyglutamine expansion in the huntingtin (htt) protein. Here, we report the development of a biochemically defined in vitro transcription assay that is responsive to mutant htt. We demonstrate that both gene-specific activator protein Sp1 and selective components of the core transcription apparatus, including TFIID and TFIIF, are direct targets inhibited by mutant htt in a polyglutamine-dependent manner. The RAP30 subunit of TFIIF specifically interacts with mutant htt both in vitro and in vivo to interfere with formation of the RAP30-RAP74 native complex. Importantly, overexpression of RAP30 in cultured primary striatal cells protects neurons from mutant htt-induced cellular toxicity and alleviates the transcriptional inhibition of the dopamine D2 receptor gene by mutant htt. Our results suggest a mutant htt-directed repression mechanism involving multiple specific components of the basal transcription apparatus.</p>
},
	keywords = {Animals, Biological Assay, Cell-Free System, Cells, Cercopithecus aethiops, COS Cells, Cultured, Dopamine D2, Down-Regulation, Genetic, Mice, Mutation, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Protein Binding, Protein Subunits, Rats, Receptors, Sp1 Transcription Factor, TFII, Transcription, Transcription Factor TFIID, Transcription Factors},
	issn = {0092-8674},
	doi = {10.1073/pnas.1100640108},
	author = {Zhai, Weiguo and Jeong, Hyunkyung and Cui, Libin and Krainc, Dimitri and Tjian, Robert}
}
