April 20, 2021

A meta-analysis of transcriptomic profiles from Huntington’s disease patients substantiates the pathophysiological role of CDC42, NFY, DLX1 and PRMT3

Description of robust transcriptomic alterations in Huntington’s disease is essential to identify targets for biochemical studies and drug development. Here, we analysed publicly available transcriptome data from the brain and blood of 449 HD patients and 212 healthy controls. We identified 737 and 661 genes with robustly altered mRNA levels in the brain and blood of HD patients, respectively. In the brain, a subnetwork of 320 genes strongly correlated with HD and was enriched in transport-related genes. Bioinformatical analysis of this subnetwork highlighted CDC42, PAK1, NFY, DLX1, HMGN3, and PRMT3. Moreover, we found that CREB1 can regulate 78.0 % of genes whose mRNA levels correlated with HD in the blood of patients. Our meta-analysis indicates that alterations in protein transport, metabolism, transcriptional regulation, and CDC42-mediated functions are central features of HD. Further our data substantiate the role of transcriptional regulators that have not been reported in the context of HD such as DLX1, HMGN3 and PRMT3 and strongly suggest transcriptional dysregulation of NFY and its target genes across tissues.

 bioRxiv Subject Collection: Neuroscience

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