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Your search keyword '"Melissa W. Braveman"' showing total 3 results
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3 results on '"Melissa W. Braveman"'

1. Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease

Author

Alice S. Chen-Plotkin, Ghazaleh Sadri-Vakili, George J. Yohrling, Melissa W. Braveman, Caroline L. Benn, Kelly E. Glajch, Derek P. DiRocco, Laurie A. Farrell, Dimitri Krainc, Silvia Gines, Marcy E. MacDonald, and Jang-Ho J. Cha

Subjects
Chromatin immunoprecipitation, Transcription, Gene regulation, Transcription factor, Huntington's disease, Polyglutamine, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
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.

Published
2006
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2. Chromatin immunoprecipitation technique for study of transcriptional dysregulation in intact mouse brain

Author

Melissa W, Braveman, Alice S, Chen-Plotkin, George J, Yohrling, and Jang-Ho J, Cha

Subjects
Mice, Transcription, Genetic, Blotting, Western, Animals, Brain, Polymerase Chain Reaction, Precipitin Tests, Chromatin
Abstract

Transcriptional dysregulation has emerged as an important pathologic mechanism underlying the pathogenesis of Huntington's disease (HD). The control of transcription depends on appropriate binding of transcription factor proteins to specific promoter regions of genes. Chromatin immunoprecipitation (ChIP) is a technique that has been used to study the association of transcription factors with DNA. To address the hypothesis that there is altered transcription factor-DNA association in HD, we have recently adapted the ChIP technique to the study of transgenic mouse brain. Here, we describe our method of performing ChIP in intact mouse brain. We have optimized conditions for formaldehyde crosslinking, antibody immunoprecipitation, and quantitative real-time polymerase chain reaction detection. Using ChIP, one can measure the association of transcription factors with specific genes and determine if this association is altered in transgenic HD mouse models. ChIP applied to whole-mouse brain can thus offer a window into mechanisms of transcriptional dysregulation.

Published
2004

3. Chromatin Immunoprecipitation Technique for Study of Transcriptional Dysregulation in Intact Mouse Brain

Author

Melissa W. Braveman, Jang-Ho J. Cha, Alice S. Chen-Plotkin, and George J. Yohrling

Subjects
Genetically modified mouse, chemistry.chemical_compound, chemistry, Transcription (biology), Immunoprecipitation, Transgene, Biology, Molecular biology, Chromatin immunoprecipitation, Gene, Transcription factor, DNA
Abstract

Transcriptional dysregulation has emerged as an important pathologic mechanism underlying the pathogenesis of Huntington's disease (HD). The control of transcription depends on appropriate binding of transcription factor proteins to specific promoter regions of genes. Chromatin immunoprecipitation (ChIP) is a technique that has been used to study the association of transcription factors with DNA. To address the hypothesis that there is altered transcription factor-DNA association in HD, we have recently adapted the ChIP technique to the study of transgenic mouse brain. Here, we describe our method of performing ChIP in intact mouse brain. We have optimized conditions for formaldehyde crosslinking, antibody immunoprecipitation, and quantitative real-time polymerase chain reaction detection. Using ChIP, one can measure the association of transcription factors with specific genes and determine if this association is altered in transgenic HD mouse models. ChIP applied to whole-mouse brain can thus offer a window into mechanisms of transcriptional dysregulation.

Published
2004
Full Text
View/download PDF

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