Dataset Information

HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration

ABSTRACT: We have developed a web-based platform for HTT PPI visualization, exploration, and multi-omic integration called HTT-OMNI. We demonstrate the utility of this platform not only for exploring and filtering existing huntingtin (HTT) PPIs, but also for investigating user-generated omics datasets. For example, we demonstrate the comparison of a published HTT IP-MS experiment, performed in the striatum brain region of a mouse HD model, to unpublished HTT IP-MS experiments in the cortex brain region. Overall, HTT-OMNI summarizes and integrates known HTT PPIs with polyQ-dependent transcriptome and proteome measurements, providing an all-in-one exploratory platform that facilitates the prioritization of target genes that may contribute to HD pathogenesis.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Todd Greco

LAB HEAD: Ileana M Cristea

PROVIDER: PXD034158 | Pride | 2022-08-15

REPOSITORIES: Pride

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Publications

HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration.

Kennedy Michelle A MA Greco Todd M TM Song Bokai B Cristea Ileana M IM

Molecular & cellular proteomics : MCP 20220803 10

Huntington's disease (HD) is a progressive neurological disorder that is caused by polyglutamine expansion of the huntingtin (HTT) protein. With the hope to uncover key modifiers of disease, a focus of the field of HD research has been on characterizing HTT-interacting proteins (HIPs) and the effect of the HTT polyglutamine expansion on the cellular omics landscape. However, while hundreds of studies have uncovered over 3000 potential HIPs to date, a means to interrogate these complementary inte ...[more]

PMID: 35932982

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Project description:Despite extensive progress in Huntingtonâ??s Disease (HD) research, very little is known about the association of epigenetic variation and HD pathogenesis in human brain tissues. Moreover, its contribution to the tissue-specific transcriptional regulation of the huntingtin gene (HTT), in which HTT expression levels are highest in brain and testes, is currently unknown. To investigate the role of DNA methylation in HD pathogenesis and tissue-specific expression of HTT, we utilized the Illumina HumanMethylation450K BeadChip array to measure DNA methylation in a cohort of age-matched HD and control human cortex and liver tissues. In cortex samples, we found minimal evidence of HD-associated DNA methylation at probed sites after correction for cell heterogeneity but did observe an association to age of disease onset. By contrast, comparison of matched cortex and liver samples revealed tissue-specific DNA methylation of the HTT gene region at 38 sites (FDR < 0.05). Importantly, we identified a novel differentially methylated binding site in the HTT proximal promoter for the transcription factor CTCF. This CTCF site displayed increased occupancy in cortex, where HTT expression is higher, compared to liver. Additionally, CTCF silencing reduced the activity of a HTT promoter-reporter construct, suggesting that CTCF plays a role in regulating HTT promoter function. Overall, although we were unable to detect HD-associated DNA methylation alterations at queried sites, we found that DNA methylation may be correlated to age of disease onset in cortex tissues. Moreover, our data suggest that DNA methylation may, in part, contribute to tissue-specific HTT transcription through differential CTCF occupancy. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain genome-wide DNA methylation measures in human cortex tissue (n = 13), with a subset of matched liver tissues (n = 5) , from a cohort of HD (n = 7) and control (n = 6) individuals in order to identify potential HD-related DNA methylation aberration in the brain as well as tissue-specific DNA methylation variation at the HTT gene locus.

Dataset Information

HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration

Publications

HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration.

Similar Datasets

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