STAT1 epigenetically regulates LCP2 and TNFAIP2 by recruiting EP300 to contribute to the pathogenesis of inflammatory bowel disease

Yu, Yanxia; Chen, Meng; Zhu, Hua; Zhuo, Mingxing; Chen, Ping; Mao, Yujuan; Li, Lianyun; Zhao, Qiu; Wu, Min; Ye, Mei

doi:10.1186/s13148-021-01101-w

Cited by 33 publications

(15 citation statements)

References 48 publications

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“…One possible explanation is that LCP2 is a target gene of STAT1. Upon activation by IFN-γ, STAT1 translocates to the nucleus and interacts with the enhancers of LCP2 and TNFAIP2.EP300 collaborates with p-STAT1 to enhance H3K27ac levels on the enhancer, leading to the transcription of LCP2 and TNFAIP2 and ultimately facilitating the progression of chronic in ammation (31). The intestinal barrier is remodeled by a signi cant group of enzymes called matrix metalloproteinases (MMPs) that can break down extracellular matrix (ECM) and basement membrane components (32).…”

Section: Discussionmentioning

confidence: 99%

Exploring the potential common genetic characteristics and molecular mechanisms between inflammatory bowel disease and atherosclerosis using bioinformatics analysis and machine learning

xuezhu,

zhai,

Rong

et al. 2023

Preprint

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Background The prevalence of inflammatory bowel disease (IBD) is increasing worldwide. According to recent research, IBD is a separate risk element for atherosclerosis (AS),however the cause of IBD combined with AS is still not clear. Through a thorough bioinformatics analysis, this study investigated the potential mechanisms of AS in conjunction with IBD and aimed to pinpoint biomarkers for patients with IBD and AS complications. Methods From two microarray datasets, we obtained differentially expressed genes(DEGs) for AS and IBD using the "Limma" package. The CDEGs underwent enrichment analysis, leading to the construction of a network for protein-protein interaction (PPI). Afterward, two algorithms based on machine learning were utilized to search for hub genes. A diagnostic nomogram was created using the Hub genes. To assess the dependability of the nomogram, the ROC curve was employed.qPCR was used to analyze the expression of hub genes in animal models. The AS dataset underwent immune infiltration analysis and consensus clustering analysis in the end. Results A total of 51 CDEGs were obtained. Further screening yielded three hub genes (LCP2, MMP9, and NCF2). The nomogram demonstrated good diagnostic performance. The disease group exhibited markedly elevated expression levels of hub genes compared to the control group, as revealed by the qPCR findings.In AS, the analysis of immune infiltration showed irregularity in the infiltration of immune cell. Two molecular subtypes were identified through consensus clustering analysis, with subtype B exhibiting higher expression levels of hub genes and immune checkpoint genes compared to subtype A. Conclusion Our study revealed the common inflammatory immune pathways in IBD and AS and constructed a nomogram with good diagnostic performance based on hub genes.

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Section: Discussionmentioning

confidence: 99%

Exploring the potential common genetic characteristics and molecular mechanisms between inflammatory bowel disease and atherosclerosis using bioinformatics analysis and machine learning

xuezhu,

zhai,

Rong

et al. 2023

Preprint

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“…Therefore, p300 may regulate the expression of granzyme B, which being important for the cytotoxicity of CD8+ T cells 14 . Another study revealed that p300 interacting with signal transducer and activator of transcription 1 could increase the H3K27ac level in the enhancers of TNFAIP2 and LCP2, which may contribute to the development of inflammatory bowel disease, and the p300 inhibitor significantly inhibited the disease in an acute colitis mice model 15 …”

Section: Discussionmentioning

confidence: 99%

“…SAA-severe aplastic anemia; R-SAA-remission SAA patients F I G U R E 5 Correlation between (A) EP300, (B) CREBBP mRNA expression in peripheral blood CD8+ T cells, and clinical parameters of bone marrow in SAA and R-SAA patients. SAA-severe aplastic anemia; R-SAA-remission SAA patients contribute to the development of inflammatory bowel disease, and the p300 inhibitor significantly inhibited the disease in an acute colitis mice model 15.…”

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confidence: 99%

Abnormal expression of histone acetylases in CD8+ T cells of patients with severe aplastic anemia

Wang

et al. 2022

Clinical Laboratory Analysis

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Introduction We aimed to investigate the balance between the mRNA levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in CD8+ T cells of patients with severe aplastic anemia (SAA). Methods Twenty untreated SAA patients, 18 remission SAA patients (R‐SAA), and 22 normal controls were evaluated. The mRNA expression levels of HATs, HDACs, and IFNG in CD8+ T cells were measured by real‐time quantitative reverse transcription polymerase chain reaction. Results Histone acetylase EP300 and CREBBP mRNA levels were significantly elevated in CD8+ T cells of SAA patients compared with the normal controls (both p < 0.05). No significant differences were observed in HDAC1 and HDAC7 mRNA between SAA patients and the normal controls. There was an obvious positive correlation between IFNG and EP300 (r = 0.5126, p < 0.01), and CREBBP (r = 0.4663, p < 0.05), respectively, in SAA and R‐SAA patients. In addition, EP300 and CREBBP mRNA levels were clearly correlated with clinical parameters of peripheral blood and bone marrow in those patients. Conclusion Our findings suggest that EP300 and CREBBP are increased in CD8+ T cells of SAA patients and are correlated with disease severity. The imbalances in HATs and HDACs may play a role in activating CD8+ T cells to promote the immune pathogenesis of SAA.

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“…After recovery from the procedure, the mice were returned to their cages. Mice (n = 5) was intraperitoneally injected with P300 inhibitor (C646, 1 mg/kg) 15 min after the procedure 29 . No mortality was observed during the procedure and during the 28 days following the procedure.…”

Section: Methodsmentioning

confidence: 99%

Sevoflurane‐induced P300 promotes neuron apoptosis via Sp1/CDK9 pathway

Zhou

Liu

Xia

2023

Clin Exp Pharma Physio

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Exposure to sevoflurane leads to serious neurological side effects, including neuronal apoptosis and cognitive impairment. In the mouse model, cyclin dependent kinase 9 (CDK9) was significantly downregulated after exposure to sevoflurane, but the effect of CDK9 on neuronal apoptosis and cognitive impairment after sevoflurane exposure has not been elucidated. Here, we found that the upregulation of P300 by sevoflurane in vitro and in vivo inhibited the expression of CDK9 and induced neuron apoptosis. The effect of sevoflurane on CDK9 expression is based on inhibition of its transcription process. P300 inhibited the binding of Sp1 to DNA by affecting the level of Sp1 acetylation, thereby inhibiting the expression of CDK9, cell‐cycle arrest and increasing neuron apoptosis. After the use of P300 inhibitor, the acetylation level of Sp1 decreased, thereby increasing binding in the CDK9 promoter region and exerting anti‐apoptosis effects. Mice exposed to sevoflurane using P300 inhibitor also showed decreased levels of apoptosis of cortical cells and a decrease in recent cognitive impairment. In summary, sevoflurane‐induced P300 inhibited activity of Sp1 by increasing Sp1 acetylation modification, down‐modulates CDK9 expression and promotes the occurrence of neuronal apoptosis.

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STAT1 epigenetically regulates LCP2 and TNFAIP2 by recruiting EP300 to contribute to the pathogenesis of inflammatory bowel disease

Cited by 33 publications

References 48 publications

Exploring the potential common genetic characteristics and molecular mechanisms between inflammatory bowel disease and atherosclerosis using bioinformatics analysis and machine learning

Exploring the potential common genetic characteristics and molecular mechanisms between inflammatory bowel disease and atherosclerosis using bioinformatics analysis and machine learning

Abnormal expression of histone acetylases in CD8+ T cells of patients with severe aplastic anemia

Sevoflurane‐induced P300 promotes neuron apoptosis via Sp1/CDK9 pathway

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