Arid1a regulates insulin sensitivity and lipid metabolism

Qu, Yue; Deng, Chuan-Huai; Luo, Qing; Shang, Xueying; Wu, Jiaoxiang; Shi, Yi; Wang, Lan; Han, Ze‐Guang

doi:10.1016/j.ebiom.2019.03.021

Cited by 35 publications

(22 citation statements)

References 35 publications

(38 reference statements)

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“…However, the mechanism of functional genome alterations in AD requires further investigation. Recent advances in chromatin profiling, especially genome-wide chromatin accessibility profiling methodologies, including MNase-seq, DNase-seq, FAIRE-seq, and ATAC-seq, have made it possible to analyze the alterations in the accessible chromatin state and allow us to better understand the molecular mechanisms of numerous diseases such as cancer, malaria, and metabolic disorders [44][45][46][47]. Although DNase-seq and MNase-seq can provide some subsets of the information obtained by ATAC-seq, they still have some limitations, for example large cell numbers, longer experimental time, and limited applicability to many systems.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the chromatin accessibility in an Alzheimer’s disease (AD) mouse model

et al. 2020

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Background: The pathological hallmarks of Alzheimer's disease (AD) involve alterations in the expression of numerous genes associated with transcriptional levels, which are determined by chromatin accessibility. Here, the landscape of chromatin accessibility was studied to understand the outline of the transcription and expression of AD-associated metabolism genes in an AD mouse model. Methods: The assay for transposase-accessible chromatin by sequencing (ATAC-seq) was used to investigate the ADassociated chromatin reshaping in the APPswe/PS1dE9 (APP/PS1) mouse model. ATAC-seq data in the hippocampus of 8-month-old APP/PS1 mice were generated, and the relationship between chromatin accessibility and gene expression was analyzed in combination with RNA sequencing. Gene ontology (GO) analysis was applied to elucidate biological processes and signaling pathways altered in APP/PS1 mice. Critical transcription factors were identified; alterations in chromatin accessibility were further confirmed using chromatin immunoprecipitation assays. Results: We identified 1690 increased AD-associated chromatin-accessible regions in the hippocampal tissues of APP/ PS1 mice. These regions were enriched in genes related to diverse signaling pathways, including the PI3K-Akt, Hippo, TGF-β, and Jak-Stat signaling pathways, which play essential roles in regulating cell proliferation, apoptosis, and inflammatory responses. A total of 1003 decreased chromatin-accessible regions were considered to be related with declined AD-associated biological processes including cellular response to hyperoxia and insulin stimulus, synaptic transmission, and positive regulation of autophagy. In the APP/PS1 hippocampus, 1090 genes were found to be upregulated and 1081 downregulated. Interestingly, enhanced ATAC-seq signal was found in approximately 740 genes, with 43 exhibiting upregulated mRNA levels. Several genes involved in AD development were found to have a significantly increased expression in APP/PS1 mice compared to controls, including Sele, Clec7a, Cst7, and Ccr6. The signatures of numerous transcription factors, including Olig2, NeuroD1, TCF4, and NeuroG2, were found enriched in the AD-associated accessible chromatin regions. The transcription-activating marks of H3K4me3 and H3K27ac were also found increased in the promoters of these genes. These results indicate that the mechanism for the upregulation of genes could be attributed to the enrichment of open chromatin regions with transcription factors motifs and the histone marks H3K4me3 and H3K27ac.

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Section: Discussionmentioning

confidence: 99%

Characterization of the chromatin accessibility in an Alzheimer’s disease (AD) mouse model

et al. 2020

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“…Glucose-tolerance test (GTT) and Insulin-tolerance test (ITT) were carried out as previously described with minor modification (Qu et al, 2019). Glucose-tolerance test (GTT) was conducted on mice that were fasted overnight (12 h).…”

Section: Tolerance Testsmentioning

confidence: 99%

miR-378b Regulates Insulin Sensitivity by Targeting Insulin Receptor and p110α in Alcohol-Induced Hepatic Steatosis

Zhong

Cheng

et al. 2020

Front. Pharmacol.

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Insulin resistance has been implicated in alcoholic liver disease. A previous study has shown that microRNAs (miRNAs) play a major role in the production, secretion, and function of insulin. MiRNAs are capable of repressing multiple target genes that in turn negatively regulate various physiological and pathological activities. However, current information on the biological function of miRNAs in insulin resistance is limited. The goal of the present study was to elucidate the role of miR-378b in alcohol-induced hepatic insulin resistance and its underlying mechanism. This study has observed that miR-378b is upregulated in National Institute on Alcohol Abuse and Alcoholism (NIAAA) alcoholic mouse models as well as in ethanol-induced L-02 cells in vitro. Furthermore, miR-378b overexpression impaired the insulin signaling pathway, and inhibition of miR-378b improved insulin sensitivity in vivo and in vitro. A mechanistic study revealed that IR and p110a are direct targets of miR-378b. Together, these results suggest that miR-378b controls insulin sensitivity by targeting the insulin receptor (IR) as well as p110a and possibly play an inhibitory role in the development of insulin resistance, thereby providing insights into the development of novel diagnostic and treatment methods.

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“…Nonalcoholic fatty liver disease (NAFLD) represents a common chronic liver disease in many developing and developed countries [ 1 ]. The prevalence of NAFLD is 20–40% in adult, while approximately 70–80% of occurrence in diabetic and obesity patients.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA expression profiles and features in NAFLD mice: a study using RNA-seq data

Yuan

Diao

et al. 2020

J Transl Med

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Background Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously. Methods A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development. Conclusions Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.

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Arid1a regulates insulin sensitivity and lipid metabolism

Cited by 35 publications

References 35 publications

Characterization of the chromatin accessibility in an Alzheimer’s disease (AD) mouse model

Characterization of the chromatin accessibility in an Alzheimer’s disease (AD) mouse model

miR-378b Regulates Insulin Sensitivity by Targeting Insulin Receptor and p110α in Alcohol-Induced Hepatic Steatosis

Circular RNA expression profiles and features in NAFLD mice: a study using RNA-seq data

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