Abstract
In polyglutamine diseases including Huntington’s disease, the causative gene products containing expanded polyglutamine form nuclear aggregates in neurons. Recent studies have identified several transcriptional factors, which interact with and are sequestered by expanded polyglutamine aggregates in neurons. Further, altered expression of many genes has been shown in several polyglutamine disease models. These observations suggest an involvement of transcriptional dysregulation in pathological process of these diseases. In this chapter, we introduce several methods to examine the interaction of transcriptional factors with and their sequestration by expanded polyglutamine proteins in vitro and in vivo.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
The Huntington’s Disease Collaborative Research and Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983
Landles C, Bates GP (2004) Huntingtin and the molecular pathogenesis of Huntington’s disease. Fourth in molecular medicine review series. EMBO Rep 5:958–963
Li SH, Li XJ (2004) Huntingtin-protein interactions and the pathogenesis of Huntington’s disease. Trends Genet 20:146–154
Harjes P, Wanker EE (2003) The hunt for huntingtin function: interaction partners tell many different stories. Trends Biochem Sci 28:425–433
Luthi-Carter R, Hanson SA, Strand AD, Bergstrom DA, Chun W, Peters NL, Woods AM, Chan EY, Kooperberg C, Krainc D, Young AB, Tapscott SJ, Olson JM (2002) Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain. Hum Mol Genet 11:1911–1926
Chan EY, Luthi-Carter R, Strand A, Solano SM, Hanson SA, DeJohn MM, Kooperberg C, Chase KO, DiFiglia M, Young AB, Leavitt BR, Cha JH, Aronin N, Hayden MR, Olson JM (2002) Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington’s disease. Hum Mol Genet 11:1939–1951
Kotliarova S, Jana NR, Sakamoto N, Kurosawa M, Miyazaki H, Nekooki M, Doi H, Machida Y, Wong HK, Suzuki T, Uchikawa C, Kotliarov Y, Uchida K, Nagao Y, Nagaoka U, Tamaoka A, Oyanagi K, Oyama F, Nukina N (2005) Decreased expression of hypotha-lamic neuropeptides in Huntington disease transgenic mice with expanded polyglutamine-EGFP fluorescent aggregates. J Neurochem 93:641–653
Sugars KL, Rubinsztein DC (2003) Transcriptional abnormalities in Huntington disease. Trends Genet 19:233–238
Riley BE, Orr HT (2006) Polyglutamine neurodegenerative diseases and regulation of transcription: assembling the puzzle. Genes Dev 20:2183–2192
Cha JH (2000) Transcriptional dysregulation in Huntington’s disease. Trends Neurosci 23:387–392
Yamanaka T, Miyazaki H, Oyama F, Kurosawa M, Washizu C, Doi H, Nukina N (2008) Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor. EMBO J 27:827–839
Doi H, Mitsui K, Kurosawa M, Machida Y, Kuroiwa Y, Nukina N (2004) Identification of ubiquitin-interacting proteins in purified polyglutamine aggregates. FEBS Lett 571:171–176
Busch A, Engemann S, Lurz R, Okazawa H, Lehrach H, Wanker EE (2003) Mutant huntingtin promotes the fibrillogenesis of wild-type huntingtin: a potential mechanism for loss of huntingtin function in Huntington’s disease. J Biol Chem 278:41452–41461
Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lehrach H, Wanker EE (1997) Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 90:549–558
Mosser DD, Theodorakis NG, Morimoto RI (1988) Coordinate changes in heat shock element-binding activity and HSP70 gene transcription rates in human cells. Mol Cell Biol 8:4736–4744
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Yamanaka, T., Nukina, N. (2010). Transcription Factor Sequestration by Polyglutamine Proteins. In: Bross, P., Gregersen, N. (eds) Protein Misfolding and Cellular Stress in Disease and Aging. Methods in Molecular Biology, vol 648. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-756-3_14
Download citation
DOI: https://doi.org/10.1007/978-1-60761-756-3_14
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-755-6
Online ISBN: 978-1-60761-756-3
eBook Packages: Springer Protocols