The modulation of GLI2, an oncogenic transcription factor commonly upregulated in cancer, is in many cases not due to genetic defects, suggesting dysregulation through alternative mechanisms. The identity of these molecular events remains for the most part unknown. Here, we identified TFII-I as a novel repressor of GLI2 expression. Mapping experiments suggest that the INR region of the GLI2 promoter is necessary for GLI2 repression. ChIP studies showed that TFII-I binds to this INR. TFII-I knockdown decreased the binding of NELF-A, a component of the promoter-proximal pausing complex at this site, and enriched phosphorylated RNAPII serine 2 in the GLI2 gene body. Immunoprecipitation studies demonstrate TFII-I interaction with SPT5, another pausing complex component. TFII-I overexpression antagonized GLI2 induction by TGFβ, a known activator of GLI2 in cancer cells. TGFβ reduced endogenous TFII-I binding to the INR and increased RNAPII SerP2 in the gene body. We demonstrate that this regulatory mechanism is not exclusive of GLI2. TGFβ-induced genes CCR7, TGFβ1 and EGR3 showed similar decreased TFII-I and NELF-A INR binding and increased RNAPII SerP2 in the gene body post-TGFβ treatment. Together these results identify TFII-I as a novel repressor of a subset of TGFβ-responsive genes through the regulation of RNAPII pausing.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367210 | PMC |
| http://dx.doi.org/10.1093/nar/gkaa476 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
m5C methylation modification may be an accomplice in colorectal cancer escaping from anti-tumor effects of innate immunity-type I/III interferon.
Front Immunol
January 2025
Traditional Chinese Medicine Department of Orthopaedic and Traumatic, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Colorectal cancer (CRC) is one of the most prevalent malignant tumors in the world, and its occurrence and development are closely related to the complex immune regulatory mechanisms. As the first barrier of the body's defense, innate immunity plays a key role in tumor immune surveillance and anti-tumor response, in which type I/III interferon (IFN) is an important mediator with significant antiviral and anti-tumor functions. 5-methylcytosine (m5C) modification of RNA is a key epigenetic regulation that promotes the expression of CRC oncogenes and immune-related genes.
View Article and Find Full Text PDFInfiltrating lipid-rich macrophage subpopulations identified as a regulator of increasing prostate size in human benign prostatic hyperplasia.
Front Immunol
January 2025
Division of Urology, Department of Surgery, Endeavor Health (formerly NorthShore University HealthSystem), Evanston, IL, United States.
Introduction: Macrophages exhibit marked phenotypic heterogeneity within and across disease states, with lipid metabolic reprogramming contributing to macrophage activation and heterogeneity. Chronic inflammation has been observed in human benign prostatic hyperplasia (BPH) tissues, however macrophage activation states and their contributions to this hyperplastic disease have not been defined. We postulated that a shift in macrophage phenotypes with increasing prostate size could involve metabolic alterations resulting in prostatic epithelial or stromal hyperplasia.
View Article and Find Full Text PDFLactate-induced protein lactylation in cancer: functions, biomarkers and immunotherapy strategies.
Front Immunol
January 2025
Department of Medical Laboratory, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.
Lactate, long viewed as a byproduct of glycolysis and metabolic waste. Initially identified within the context of yogurt fermentation, lactate's role extends beyond culinary applications to its significance in biochemical processes. Contemporary research reveals that lactate functions not merely as the terminal product of glycolysis but also as a nexus for initiating physiological and pathological responses within the body.
View Article and Find Full Text PDFPlasma protein levels provide important insights into human disease, yet a comprehensive assessment of plasma proteomics across organs is lacking. Using large-scale multimodal data from the UK Biobank, we integrated plasma proteomics with organ imaging to map their phenotypic and genetic links, analyzing 2,923 proteins and 1,051 imaging traits across multiple organs. We uncovered 5,067 phenotypic protein-imaging associations, identifying both organ-specific and organ-shared proteomic relations, along with their enriched protein-protein interaction networks and biological pathways.
View Article and Find Full Text PDFCollaborative Effects of Caloric Restriction and Quercetin on Age-related Oxidative Stress Reduction through NQO1/Sirt1 Gene Regulation.
Int J Prev Med
December 2024
Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Background: Aging is caused by the progressive accumulation of various changes in the body, which is associated with an increase in free radicals and oxidative stress (OS). The aim of this study was to investigate the potential of caloric restriction (CR) and quercetin (QUER) in alleviating OS in aging and the involvement of the NAD (P) H quinone oxidoreductase 1 (NQO1)/SIRT1 signaling pathway in these effects.
Methods: Two age groups of male Wistar rats (eight and 20 weeks of age) were included in the study and subdivided into normal diet (ND), ND with QUER (15 mg Kg, IP), ND with CR, and ND with QUER and CR groups.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!