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Tissue Specific Methylation and Expression Patterns of ADCA-DN Patients

ABSTRACT: Tissue Specific Methylation and Expression Patterns of ADCA-DN Patients

PROVIDER: PRJNA523617 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8606210_1.fastq.gz	Fastqsanger.gz
	SRR8606210_2.fastq.gz	Fastqsanger.gz
	SRR8606220_1.fastq.gz	Fastqsanger.gz
	SRR8606220_2.fastq.gz	Fastqsanger.gz
	SRR8606230_1.fastq.gz	Fastqsanger.gz

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Tissue Specific Methylation and Expression Patterns of ADCA-DN Patients

Project description:Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) is a late onset disorder, due to mutations in DNA methyltransferase type 1 (DNMT1). Yet our understanding of how these mutations in DNMT1 lead to the clinical phenotypes of ADCA-DN is still unclear. To address this, we used fibroblasts, induced pluripotent stem cells (iPSCs) and induced neurons (iNs) generated from patients with ADCA-DN and controls, to determine the underlining epigenomic changes. Here we show that the differential expression pattern and differential methylation spectrum between patients and controls were tissue-specific. Furthermore, methylation and gene expression changes were negatively correlated in iPSCs and iNs. In addition, we identified a group of genes associated with clinical phenotypes of ADCA-DN, including PDGFB and PRDM8 for cerebellar ataxia, psychosis and dementia, and NR2F1 for deafness and optic atrophy. We further showed that ZFP57, which is required to maintain gene imprinting through DNA methylation during early development, was hypomethylated in promoters and exhibited upregulated expression in patients with ADCA-DN in both iPSC and iNs. Our results provide insight into the molecular changes associated with ADCA-DN, with potential implications for genes associated with related phenotypes.

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