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

ABSTRACT: Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington’s disease [RNA-seq]

PROVIDER: PRJNA587147 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10386764.fastq.gz	Fastqsanger.gz
	SRR10386764_1.fastq.gz	Fastqsanger.gz
	SRR10386764_2.fastq.gz	Fastqsanger.gz
	SRR10386765.fastq.gz	Fastqsanger.gz
	SRR10386765_1.fastq.gz	Fastqsanger.gz

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

Project description:Huntington’s disease (HD) is a chronic neurodegenerative disorder characterized by a late clinical onset despite ubiquitous expression of the mutant Huntingtin gene (HTT) from birth. Transcriptional dysregulation is a pivotal feature of HD. Yet, the genes that are altered in the prodromal period and their regulators, which present opportunities for therapeutic intervention, remain to be elucidated. Using transcriptional and chromatin profiling, we found aberrant transcription and changes in histone H3K27 acetylation in the striatum of R6/1 mice during the presymptomatic disease stages. Integrating these data, we identified the Elk-1 transcription factor as a candidate regulator of prodromal changes in HD. Exogenous expression of Elk-1 exerted beneficial effects in a primary striatal cell culture model of HD, and adeno-associated virus-mediated Elk-1 overexpression alleviated transcriptional dysregulation in R6/1 mice. Collectively, our work demonstrates that aberrant gene expression precedes overt disease onset in HD, identifies the Elk-1 transcription factor as a key regulator linked to early epigenetic and transcriptional changes in HD, and presents evidence for Elk-1 as a target for alleviating molecular pathology in HD.

2019-11-19 | GSE139847 | GEO

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

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

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

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

Project description:Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington’s disease [ChIP-seq]

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-11-19 | GSE140118 | GEO

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

Project description:Huntington's disease (HD) is a chronic neurodegenerative disorder characterized by a late clinical onset despite ubiquitous expression of the mutant Huntingtin gene (HTT) from birth. Transcriptional dysregulation is a pivotal feature of HD. Yet, the genes that are altered in the prodromal period and their regulators, which present opportunities for therapeutic intervention, remain to be elucidated. Using transcriptional and chromatin profiling, we found aberrant transcription and changes in histone H3K27acetylation in the striatum of R6/1 mice during the presymptomatic disease stages. Integrating these data, we identified the Elk-1 transcription factor as a candidate regulator of prodromal changes in HD. Exogenous expression of Elk-1 exerted beneficial effects in a primary striatal cell culture model of HD, and adeno-associated virus-mediated Elk-1 overexpression alleviated transcriptional dysregulation in R6/1 mice. Collectively, our work demonstrates that aberrant gene expression precedes overt disease onset in HD, identifies the Elk-1 transcription factor as a key regulator linked to early epigenetic and transcriptional changes in HD, and presents evidence for Elk-1 as a target for alleviating molecular pathology in HD.

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