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

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

PROVIDER: PRJNA588292 | 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]

2019-11-19 | GSE140117 | GEO

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

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

| PRJNA587147 | ENA

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]

| PRJNA588294 | ENA

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.

| S-EPMC6900520 | biostudies-literature

Expression data from WT and ELK-1 overexpressing stem cells

Project description:Two ELK-1 overexpressing cells were generated from CSES7 cell line and compared to WT CSES7. We used microarrays to study the gene expression profiles of the ELK-1 overexpressing cells in order to identify ELK-1 target genes that might be involve in the processes of apoptosis and differentiation

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Systemic Epigenome-Wide Association Study of Elk Treponeme- Associated Hoof Disease

Project description:Treponeme-associated hoof disease (TAHD) is an emerging disease of elk (Cervus canadensis) in the U.S. Pacific West. Because environmental epigenetics is the primary molecular process that mediates environmental factor impacts on a host organism and disease, the role of epigenetics in TAHD etiology was examined. The current study was designed to examine potential effects of TAHD on systemic epigenetic modifications in infected elk over a range of TAHD lesion severity. Leg tendons that contain predominantly fibroblast connective tissue cells were used to isolate fibroblast cells for epigenetic analysis in unaffected and TAHD-positive male and female Roosevelt and Rocky Mountain elk. DNA methylation in the tendon cells in the different groups was examined. Differential DNA methylation regions (DMRs) between the unaffected and TAHD-positive were identified for both female and male elk. The presence of TAHD was associated with alteration of the connective tissue cell epigenetics and DMR associated genes identified. Therefore, the infected elk were found to have a systemic epigenetic alteration that was associated with the disease despite TAHD pathology being generally limited to feet. Other cell populations with the elk are also anticipated to be affected, and if the elk germline epigenetics is altered then generational transmission of susceptibility to TAHD may impact subsequent generations through epigenetic inheritance. This first study of epigenetic changes associated with disease in elk suggests that TAHD promotes a systemic effect on the elk epigenetics which could exert health impacts on the elk.

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Expression data from WT and ELK-1 overexpressing stem cells

2013-07-12 | E-GEOD-48792 | biostudies-arrayexpress

Elk Gut Metagenome

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| PRJNA629905 | ENA