Dataset Information

Integration of ATAC-Seq and RNA-Seq identifies key genes and pathways involved in the neuroprotection of S-adenosylmethionine against perioperative neurocognitive disorder.

ABSTRACT: The gene-regulatory landscape is highly dynamic in healthy and diseased brains. DNA methylation is a well-known epigenetic modification that regulates gene expression, and our previous study demonstrated that S-adenosylmethionine (SAM), a methylome modulator, was a neuroprotectant against perioperative neurocognitive disorder (PND). However, the underlying mechanism remains to be elucidated. Here, we integrated an assay for transposase-accessible chromatin by sequencing (ATAC-seq) and RNA sequencing (RNA-seq) to identify the key genes and pathways involved in the neuroprotection of SAM against PND. Our RNA-seq data demonstrated that genes involved in biological processes such as Wnt signaling, inflammatory response, transcription and long-term potentiation likely mediate the neuroprotection of SAM. Our ATAC-seq data provided comprehensive maps of chromatin accessibility changes induced by laparotomy and laparotomy + SAM treatment, and functional annotation of the regions with high variations in chromatin accessibility highlighted the role of the Wnt signaling pathway in PND pathogenesis and SAM treatment. Further motif analysis identified key transcription factors (e.g., CTCF, TFDP1, TCFL5, KLF15, ZBTB14, TFAP2E) that may participate in the neuroprotection of SAM. In conclusion, the current study provides an epigenomic perspective to understand the pathogenesis of PND and its treatment by SAM.

SUBMITTER: Xu F

PROVIDER: S-EPMC10024148 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Integration of ATAC-Seq and RNA-Seq identifies key genes and pathways involved in the neuroprotection of S-adenosylmethionine against perioperative neurocognitive disorder.

Xu Feifei F Cong Peilin P Lu Zhihong Z Shi Liwen L Xiong Lize L Zhao Guanghou G

Computational and structural biotechnology journal 20230303

The gene-regulatory landscape is highly dynamic in healthy and diseased brains. DNA methylation is a well-known epigenetic modification that regulates gene expression, and our previous study demonstrated that S-adenosylmethionine (SAM), a methylome modulator, was a neuroprotectant against perioperative neurocognitive disorder (PND). However, the underlying mechanism remains to be elucidated. Here, we integrated an assay for transposase-accessible chromatin by sequencing (ATAC-seq) and RNA sequen ...[more]

PMID: 36942104

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Project description:ObjectiveAlthough glucagon-secreting α-cells and insulin-secreting β-cells have opposing functions in regulating plasma glucose levels, the two cell types share a common developmental origin and exhibit overlapping transcriptomes and epigenomes. Notably, destruction of β-cells can stimulate repopulation via transdifferentiation of α-cells, at least in mice, suggesting plasticity between these cell fates. Furthermore, dysfunction of both α- and β-cells contributes to the pathophysiology of type 1 and type 2 diabetes, and β-cell de-differentiation has been proposed to contribute to type 2 diabetes. Our objective was to delineate the molecular properties that maintain islet cell type specification yet allow for cellular plasticity. We hypothesized that correlating cell type-specific transcriptomes with an atlas of open chromatin will identify novel genes and transcriptional regulatory elements such as enhancers involved in α- and β-cell specification and plasticity.MethodsWe sorted human α- and β-cells and performed the "Assay for Transposase-Accessible Chromatin with high throughput sequencing" (ATAC-seq) and mRNA-seq, followed by integrative analysis to identify cell type-selective gene regulatory regions.ResultsWe identified numerous transcripts with either α-cell- or β-cell-selective expression and discovered the cell type-selective open chromatin regions that correlate with these gene activation patterns. We confirmed cell type-selective expression on the protein level for two of the top hits from our screen. The "group specific protein" (GC; or vitamin D binding protein) was restricted to α-cells, while CHODL (chondrolectin) immunoreactivity was only present in β-cells. Furthermore, α-cell- and β-cell-selective ATAC-seq peaks were identified to overlap with known binding sites for islet transcription factors, as well as with single nucleotide polymorphisms (SNPs) previously identified as risk loci for type 2 diabetes.ConclusionsWe have determined the genetic landscape of human α- and β-cells based on chromatin accessibility and transcript levels, which allowed for detection of novel α- and β-cell signature genes not previously known to be expressed in islets. Using fine-mapping of open chromatin, we have identified thousands of potential cis-regulatory elements that operate in an endocrine cell type-specific fashion.

Dataset Information

Integration of ATAC-Seq and RNA-Seq identifies key genes and pathways involved in the neuroprotection of S-adenosylmethionine against perioperative neurocognitive disorder.

Publications

Integration of ATAC-Seq and RNA-Seq identifies key genes and pathways involved in the neuroprotection of S-adenosylmethionine against perioperative neurocognitive disorder.

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