Brain-specific factors in combination with mutant huntingtin induce gene-specific transcriptional dysregulation

Geraldine T. Gomez; Haibei Hu; Elizabeth A. McCaw; Eileen M. Denovan-Wright

doi:10.1016/j.mcn.2005.12.004

Brain-specific factors in combination with mutant huntingtin induce gene-specific transcriptional dysregulation

Geraldine T. Gomez, Haibei Hu, Elizabeth A. McCaw, Eileen M. Denovan-Wright

Medicine

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

12 Citas (Scopus)

Resumen

Mutant huntingtin lowered steady-state levels of DARPP-32 mRNA in the brain but not kidney of R6 transgenic HD mice by repressing transcription from one of two promoters. The activity of DARPP-32 promoter deletion constructs were lower in the presence of mutant huntingtin in immortalized striatal cell lines but no difference in transcription factor binding to the promoter was detected. The activity of CMV, TK and HPRT promoters was also affected by mutant huntingtin in these cell lines. Transient transfection experiments demonstrated that short-term expression of mutant huntingtin exerted a cell- and promoter-specific transcriptional repression. In in vitro experiments, transcription of the CMV promoter was reduced in the presence of striatal proteins and mutant huntingtin. It is likely that select combinations of trans-acting factors, co-activators and components of the Pol II holoenzyme acting in concert provide the basis for both the gene- and tissue-specific effects of mutant huntingtin.

Idioma original	English
Páginas (desde-hasta)	661-675
Número de páginas	15
Publicación	Molecular and Cellular Neurosciences
Volumen	31
N.º	4
DOI	https://doi.org/10.1016/j.mcn.2005.12.004
Estado	Published - abr. 2006

Nota bibliográfica

Funding Information:
We would like to thank Dr. Elena Cattaneo for her generous gift of the ST14A and derivative cell lines. Min Huang, Kay Murphy and Janette Nason provided excellent technical assistance. This work was supported by a grant from the Canadian Institutes of Health Research (CIHR) to E.M.D.-W. G.T.G. holds a National Sciences and Engineering Research Council (NSERC) postgraduate scholarship and is an honorary Izaak Walton Killam Memorial Scholar. H.H. holds a Huntington Society of Canada Landmark Scholarship.

ASJC Scopus Subject Areas

Molecular Biology
Cellular and Molecular Neuroscience
Cell Biology

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title = "Brain-specific factors in combination with mutant huntingtin induce gene-specific transcriptional dysregulation",

abstract = "Mutant huntingtin lowered steady-state levels of DARPP-32 mRNA in the brain but not kidney of R6 transgenic HD mice by repressing transcription from one of two promoters. The activity of DARPP-32 promoter deletion constructs were lower in the presence of mutant huntingtin in immortalized striatal cell lines but no difference in transcription factor binding to the promoter was detected. The activity of CMV, TK and HPRT promoters was also affected by mutant huntingtin in these cell lines. Transient transfection experiments demonstrated that short-term expression of mutant huntingtin exerted a cell- and promoter-specific transcriptional repression. In in vitro experiments, transcription of the CMV promoter was reduced in the presence of striatal proteins and mutant huntingtin. It is likely that select combinations of trans-acting factors, co-activators and components of the Pol II holoenzyme acting in concert provide the basis for both the gene- and tissue-specific effects of mutant huntingtin.",

author = "Gomez, {Geraldine T.} and Haibei Hu and McCaw, {Elizabeth A.} and Denovan-Wright, {Eileen M.}",

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N2 - Mutant huntingtin lowered steady-state levels of DARPP-32 mRNA in the brain but not kidney of R6 transgenic HD mice by repressing transcription from one of two promoters. The activity of DARPP-32 promoter deletion constructs were lower in the presence of mutant huntingtin in immortalized striatal cell lines but no difference in transcription factor binding to the promoter was detected. The activity of CMV, TK and HPRT promoters was also affected by mutant huntingtin in these cell lines. Transient transfection experiments demonstrated that short-term expression of mutant huntingtin exerted a cell- and promoter-specific transcriptional repression. In in vitro experiments, transcription of the CMV promoter was reduced in the presence of striatal proteins and mutant huntingtin. It is likely that select combinations of trans-acting factors, co-activators and components of the Pol II holoenzyme acting in concert provide the basis for both the gene- and tissue-specific effects of mutant huntingtin.

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Brain-specific factors in combination with mutant huntingtin induce gene-specific transcriptional dysregulation

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Nota bibliográfica

ASJC Scopus Subject Areas

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