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The role of RPA1 in T cells [thymus]

ABSTRACT: As a single strand DNA binding protein, RPA1 participates in various cellular processes including DNA replication and DNA repair. However, the role of RPA1 in T cells is largely unknown. We generated a mouse model in which RPA1 was specifically deleted in T cells. Through single cell RNA sequencing, we reveal the immune landscape in RPA1 conditional knockout mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE189929 | GEO | 2024/06/15

REPOSITORIES: GEO

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The role of RPA1 in T cell

Project description:As a single strand DNA binding protein, RPA1 participates various cellular processes including DNA replication and DNA repair.However, the role of RPA1 in T cell is largely unknown. We generate a mice model in which RPA1 was specifically deleted in T cell. Through single cell RNA sequencing, we reveal the immune landscape in RPA1 conditional knockout mice.

2024-06-15 | GSE189548 | GEO

The role of RPA1 in T cells [spleen]

Project description:As a single strand DNA binding protein, RPA1 participates in various cellular processes including DNA replication and DNA repair. However, the role of RPA1 in T cells is largely unknown. We generated a mouse model in which RPA1 was specifically deleted in T cells. Through single cell RNA sequencing, we reveal the immune landscape in RPA1 conditional knockout mice.

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RPA1 Remodels Liver Chromatin Architecture to Maintain Lipid Metabolic Homeostasis

Project description:Replication protein A(RPA), a ssDNA binding protein complex, participates in DNA replication, recombination and damage repair, but its physiological function remains elusive. Here, we show that heterozygous Rpa1 knockout mice were developmentally normal, but hypersensitive to ageing and high-fat-diet (HFD) induced hepatic steatosis. Liver specific deletion of Rpa1 leads to impaired lipid beta-oxidation, hepatic steatosis and subsequently hepatocellular carcinoma (HCC). Assays for RNA-seq, pull-down and transposase-accessible chromatin sequencing (ATAC-seq) reveal that RPA1 is required for transcription of a subgroup of lipid metabolic genes via altering chromatin accessibility landscape. Thus, our results suggest that RPA1 is a critical regulator of gene transcription and chromatin remodeling, linking a guardian of genome stability to lipid metabolic homeostasis.

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The role of RPA1 in T cells [thymus]

Project description:The role of RPA1 in T cells [thymus]

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RPA1 controls chromatin architecture and maintains lipid metabolic homeostasis

Project description:Replication protein A1 (RPA1) is a single-stranded DNA binding protein that is known to participate in DNA replication, recombination and damage repair. However, little is known about RPA1’s role in controlling chromatin architecture and gene transcription. Further, physiological functions of RPA1 in mouse tissues still remain exclusive. Here we show that Rpa1 heterozygous mice developed age-depended fatty liver disease and are more susceptible to hepatic steatosis in response to high-fat diet. Liver specific deletion of Rpa1 impairs fatty acid oxidation, leading to hepatic steatosis and high incidence of hepatocellular carcinoma. Transcriptome analysis identified down-regulation of fatty acid oxidation related genes. Cleavage Under Targets and Tagmentation (CUT&Tag) and Assay for transposase-accessible chromatin using sequencing (ATAC-seq) revealed that RPA1 binds and regulates chromatin accessibility in regulatory regions of a group of genes involved in lipid metabolism in liver. Further, down-regulation of RPA1 was found in patients with fatty liver disease. Thus, our results not only established that RPA1 is critical controller of chromatin architecture and regulator of gene transcription, but also provided new insights into the epigenetic mechanism of fatty liver disease, which could inform future therapy.

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The Role of CDYL-Regulated Crotonylation of RPA1 in Homologous Recombination-Mediated DNA Repair

Project description:Lysine crotonylation (Kcr) is a recently-identified protein short-chain acylation. We have previously reported that chromodomain Y-like transcription corepressor CDYL acts as a crotonyl-CoA hydratase and negatively regulates histone Kcr. However, the global crotonylome of CDYL-regulated Kcr on non-histone substrates remains unclear. Using proteome-wide quantitative Kcr analysis, we identified 14,311 Kcr sites across 3,734 proteins in HeLa cells, providing by far the largest crotonylome data set from a single study. Upon depletion of CDYL, 1,141 Kcr sites from 759 proteins were increased by more than 1.5 fold, and 933 Kcr sites from 528 proteins were decreased by more than 0.67 fold. Upregulated crotonylome alterations upon CDYL depletion include components from diverse cellular pathways such as RNA splicing, DNA replication, and amino acid metabolism. Specifically, CDYL regulates K88 and K379 of crotonylation on RPA1, which affects its binding to other DNA repair factors including BLM, DNA2L, RAD50 and WRN. We showed evidence that CDYL-mediated RPA1 crotonylation is critical for the homologous recombination (HR) repair of camptothecin (CPT)-induced DNA damage. Together, our results provide a broad lysine crotonylome in response to CDYL and shed new light on the role of RPA1 Kcr in DNA repair, implicating functional importance of Kcr on non-histone substrates in diverse cellular processes.

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The role of RPA1 in T cell

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Identification of genes regulated by knockdown of HSF1 or RPA1

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Serratia marcescens strain:RPA1

Project description:Serratia marcescens RPA1 Genome sequencing and assembly

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