Dataset Information

Cell-type specific DNA methylome signatures reveal epigenetic mechanisms for neuronal diversity and neurodevelopmental disorder

ABSTRACT: We report the application of an affinity purification approach (INTACT) to isolate tagged nuclei for GABAergic (GABA), Glutamatergic (Glu), and Purkinje neurons in mice. We performed whole-genome bisulfite sequencing (WGBS) to explore the cell type-specific DNA methylation signatures for the three neuronal types, together with matched transcriptomics. We found a substantial number of differentially methylated regions (DMRs) between cell types, characterized cell-type specific DMRs, and estimated the effects of DNA methylation on gene expression. Finally, we revealed that DNA methylation altered in a cell-type specific manner in a mouse model of Rett syndrome, a neurodevelopmental disorder caused by Mecp2 loss of function. The presented data emphasize the important role of DNA methylation-mediated epigenetic regulation in neuronal diversity and disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE191211 | GEO | 2022/08/24

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Down syndrome (DS) is characterized by a genome-wide profile of differential DNA methylation that is skewed towards hypermethylation in most tissues, including brain, and includes pan-tissue differential methylation. The molecular mechanisms involve the overexpression of genes related to DNA methylation on chromosome 21. Here, we stably overexpressed the chromosome 21 gene DNA methyltransferase 3L (DNMT3L) in the human SH-SY5Y neuroblastoma cell line and assayed DNA methylation at over 26 million CpGs by whole genome bisulfite sequencing (WGBS) at three different developmental phases (undifferentiated, differentiating, and differentiated). Results: DNMT3L overexpression resulted in global CpG and CpG island hypermethylation as well as thousands of differentially methylated regions (DMRs). The DNMT3L DMRs were skewed towards hypermethylation and mapped to genes involved in neurodevelopment, cellular signaling, and gene regulation. Consensus DNMT3L DMRs showed that cell lines clustered by genotype and then differentiation phase, demonstrating sets of common genes affected across neuronal differentiation. The hypermethylated DNMT3L DMRs from all pairwise comparisons were enriched for regions of bivalent chromatin marked by H3K4me3 as well as differentially methylated sites from previous DS studies of diverse tissues. In contrast, the hypomethylated DNMT3L DMRs from all pairwise comparisons displayed a tissue-specific profile enriched for regions of heterochromatin marked by H3K9me3 during embryonic development. Conclusions: Taken together, these results support a mechanism whereby regions of bivalent chromatin that lose H3K4me3 during neuronal differentiation are targeted by excess DNMT3L and become hypermethylated. Overall, these findings demonstrate that DNMT3L overexpression during neurodevelopment recreates a facet of the genome-wide DS DNA methylation signature by targeting known genes and gene clusters that display pan-tissue differential methylation in DS.

Dataset Information

Cell-type specific DNA methylome signatures reveal epigenetic mechanisms for neuronal diversity and neurodevelopmental disorder

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets