Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington’s disease | Zendy

Ferah Yildirim | Zendy; Christopher Ng | Zendy; Vincent Kappès | Zendy; Tobias Ehrenberger | Zendy; Siobhan K. Rigby | Zendy; Victoria Stivanello | Zendy; Theresa A. Gipson | Zendy; Anthony R. Soltis | Zendy; Peter Vanhoutte | Zendy; Jocelyne Caboche | Zendy; David E. Housman | Zendy; Ernest Fraenkel | Zendy

Open Access

Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington’s disease

Author(s) -

Ferah Yildirim,

Christopher Ng,

Vincent Kappès,

Tobias Ehrenberger,

Siobhan K. Rigby,

Victoria Stivanello,

Theresa A. Gipson,

Anthony R. Soltis,

Peter Vanhoutte,

Jocelyne Caboche,

David E. Housman,

Ernest Fraenkel

Publication year - 2019

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.1908113116

Subject(s) - huntingtin , huntington's disease , transcription factor , biology , epigenetics , huntingtin protein , transcriptional regulation , chromatin , regulator , epigenomics , chromatin immunoprecipitation , gene expression , disease , gene , genetics , medicine , dna methylation , promoter

Significance Improved therapeutic intervention for neurodegenerative diseases, particularly early in progression of the disease course, is a critical need. Huntington’s disease (HD) is a paradigmatic disorder in this search in which vulnerable individuals can be identified early. This study focuses on the earliest stages of disease in a well-characterized animal model system. We identify early aberrant transcription and chromatin changes in affected brain regions of HD mice. The study identifies the Elk-1 transcription factor as a significant regulator of early transcriptional changes in HD. Enhanced Elk-1 levels exerted beneficial effects in an in vitro model and resulted in extensive restoration of transcriptional dysregulation in vivo. These results suggest a target for alleviating pathology in HD and other neuropsychiatric conditions.

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