Similar Datasets
Project description:Liver cancer, including hepatocellular carcinoma (HCC), is a malignant tumor that has high rates of metastasis and mortality worldwide. Upstream transcription factor 1 (USF1) is a canonical transcription factor (TF) and is associated with the pathogenesis of several cancers, but its biological functions and molecular targets in HCC remain unclear. Huh7 cells that overexpress USF1 were used with whole transcriptome profiling through RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing methods to investigate the downstream targets of USF1. Reverse transcription-quantitative PCR was then used to validate the downstream targets. The results showed that USF1 significantly regulates 350 differentially expressed genes (DEGs). The upregulated DEGs were primarily protein-coding genes enriched in immune and inflammation response pathways, while the downregulated DEGs were mainly coding long non-coding (lnc)RNAs, indicating the regulatory function of USF1. It was also demonstrated that USF1 directly binds to the promoter region of 2,492 genes, which may be involved in the viral progression and cell proliferation pathways. By integrating these two datasets, 16 overlapped genes were detected, including downregulated lncRNA-NEAT1 and upregulated TF-ETV5. The downregulated lncRNA-NEAT1 showed reverse expression pattern and prognosis result compared with that of USF1 in patients with liver cancer, while upregulated TF-ETV5 showed consistent results with USF1. Promoter region motif analysis indicated that ETV5 has more binding motifs and genes than USF1 itself for USF1-regulated DEGs, indicating that USF1 may indirectly modulate gene expression by regulating ETV5 expression in Huh7 cells. The study also validated the direct interaction between USF1 and the promoter of ETV5 using ChIP-qPCR. In summary, the results demonstrated that USF1 binds to the promoter region of thousands of genes and affects a large part of DEGs indirectly. Downstream genes, including lncRNA-NEAT1 and TF-ETV5, may also have potential functions in the regulated network by USF1 and have potential functions in the progression of HCC. The present findings suggested that USF1 and its downstream targets could be potential targets for HCC therapy in the future.
| S-EPMC10655063 | biostudies-literature
Project description:Liver cancer, including hepatocellular carcinoma (HCC), is a malignant tumor type with high metastasis and mortality rate in worldwide. Upstream transcription factor 1 (USF1) is a canonical transcription factor (TF) and associated with the pathogenesis of several cancers, while its biological functions and molecular targets in HCC are not clear. In this study, we overexpressed USF1 in Huh7 cells and used whole transcriptome profile sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) methods to systematically investigate the downstream targets of USF1. Following polymerase chain reaction (PCR) was used to validate the downstream targets. Based on the results, we found USF1 significantly regulated 350 differentially expressed genes (DEGs). Up DEGs were mainly protein coding genes, and enriched in immune and inflammation response pathways; while down DEGs were mainly lncRNAs, indicating the regulatory feature of USF1. We also detected USF1 directly bound to the promoter region of 2492 genes, which may deeply participate in the viral progression and cell proliferation pathways. By integrating these two datasets, we detected 16 overlapped genes, including down lncRNA-NEAT1 and up TF-ETV5. Down lncRNA-NEAT1 showed reverse expression pattern and prognosis result to USF1 in liver cancer patients, while up TF-ETV5 showed consistent result to USF1. Promoter region motif analysis indicated that ETV5 had more binding motifs and genes than USF1 itself for USF1-regulated DEGs, indicating that USF1 may indirectly modulate gene expression by regulating ETV5 expression in Huh7 cells. Finally, we validated the direct interaction between USF1 and the promoter of ETV5 using ChIP-qPCR. In summary, our results demonstrated that USF1 binds to the promoter region of thousands of genes, and affects large part of DEGs by indirectly manner. The downstream genes, including lncRNA-NEAT1 and TF-ETV5, may also tightly participate in the regulated network by USF1 and have potential functions in the progression of HCC. The USF1 and its downstream targets could be used as potential targets for HCC therapy in future.
2023-09-28 | GSE232262 | GEO
Project description:Liver cancer, including hepatocellular carcinoma (HCC), is a malignant tumor type with high metastasis and mortality rate in worldwide. Upstream transcription factor 1 (USF1) is a canonical transcription factor (TF) and associated with the pathogenesis of several cancers, while its biological functions and molecular targets in HCC are not clear. In this study, we overexpressed USF1 in Huh7 cells and used whole transcriptome profile sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) methods to systematically investigate the downstream targets of USF1. Following polymerase chain reaction (PCR) was used to validate the downstream targets. Based on the results, we found USF1 significantly regulated 350 differentially expressed genes (DEGs). Up DEGs were mainly protein coding genes, and enriched in immune and inflammation response pathways; while down DEGs were mainly lncRNAs, indicating the regulatory feature of USF1. We also detected USF1 directly bound to the promoter region of 2492 genes, which may deeply participate in the viral progression and cell proliferation pathways. By integrating these two datasets, we detected 16 overlapped genes, including down lncRNA-NEAT1 and up TF-ETV5. Down lncRNA-NEAT1 showed reverse expression pattern and prognosis result to USF1 in liver cancer patients, while up TF-ETV5 showed consistent result to USF1. Promoter region motif analysis indicated that ETV5 had more binding motifs and genes than USF1 itself for USF1-regulated DEGs, indicating that USF1 may indirectly modulate gene expression by regulating ETV5 expression in Huh7 cells. Finally, we validated the direct interaction between USF1 and the promoter of ETV5 using ChIP-qPCR. In summary, our results demonstrated that USF1 binds to the promoter region of thousands of genes, and affects large part of DEGs by indirectly manner. The downstream genes, including lncRNA-NEAT1 and TF-ETV5, may also tightly participate in the regulated network by USF1 and have potential functions in the progression of HCC. The USF1 and its downstream targets could be used as potential targets for HCC therapy in future.
2023-09-28 | GSE232261 | GEO
Project description:USF1 modulates transcription and cellular functions by regulating multiple transcription factors in Huh7 cells.
| PRJNA971498 | ENA
Project description:USF1 modulates transcription and cellular functions by regulating multiple transcription factors in Huh7 cells [RNA-seq]
| PRJNA971502 | ENA
Project description:USF1 modulates transcription and cellular functions by regulating multiple transcription factors in Huh7 cells [ChIP-seq]
| PRJNA971506 | ENA
Project description:PIWI-interacting RNAs (piRNAs) mediate transposable element (TE) silencing at the transcriptional or post-transcriptional level in animal gonads. In the Drosophila ovary, Piwiâ??piRNA complexes (Piwiâ??piRISCs) repress TE transcription by modifying the chromatin state, such as H3K9me3 marks. Here, we demonstrate that Piwi physically interacts with linker histone H1. Depletion of Piwi decreases H1 density on target loci, leading to TE derepression. Loss of H1 results in gain of chromatin accessibility at target loci without affecting H3K9me3 and heterochromatin protein 1a (HP1a) density at the same loci. Piwi-mediated TE silencing also requires HP1a by regulating chromatin accessibility through its association with target loci. Thus, Piwiâ??piRISCs require both H1 and HP1a to repress TEs, and the silencing is correlated with the state of chromatin formation rather than H3K9me3 marks. These findings suggest that Piwiâ??piRISCs regulate the interaction of chromatin components with target loci to maintain silencing of the TE state through the modulation of chromatin accessibility. RNA levels, H1 and H3K9me3 occupancy, chromatin accessibility, and Piwi-associated small RNA levels in ovarian somatic cells (OSC) depleted of piRNA pathway components and H1.
2016-06-30 | E-GEOD-81434 | biostudies-arrayexpress
Project description:The cellular bromodomain protein Brd4 functions in multiple processes of the papillomavirus life cycle, including viral replication, genome maintenance, and gene transcription through its interaction with the viral protein, E2. However, the mechanisms by which E2 and Brd4 activate viral transcription are still not completely understood. In this study, we show that recruitment of positive transcription elongation factor b (P-TEFb), a functional interaction partner of Brd4 in transcription activation, is important for E2's transcription activation activity. Furthermore, chromatin immunoprecipitation (ChIP) analyses demonstrate that P-TEFb is recruited to the actual papillomavirus episomes. We also show that E2's interaction with cellular chromatin through Brd4 correlates with its papillomavirus transcription activation function since JQ1(+), a bromodomain inhibitor that efficiently dissociates E2-Brd4 complexes from chromatin, potently reduces papillomavirus transcription. Our study identifies a specific function of Brd4 in papillomavirus gene transcription and highlights the potential use of bromodomain inhibitors as a method to disrupt the human papillomavirus (HPV) life cycle.
| S-EPMC4147693 | biostudies-literature
Project description:Proteasome activity is crucial for cellular integrity, but how tissues adjust proteasome content in response to catabolic stimuli is uncertain. Here, we demonstrate that transcriptional coordination by multiple transcription factors is required to increase proteasome content and activate proteolysis in catabolic states. Using denervated mouse muscle as a model system for accelerated proteolysis in vivo, we reveal that a two-phase transcriptional program activates genes encoding proteasome subunits and assembly chaperones to boost an increase in proteasome content. Initially, gene induction is necessary to maintain basal proteasome levels, and in a more delayed phase (7-10 days after denervation), it stimulates proteasome assembly to meet cellular demand for excessive proteolysis. Intriguingly, the transcription factors PAX4 and α-PALNRF-1 control the expression of proteasome among other genes in a combinatorial manner, driving cellular adaptation to muscle denervation. Consequently, PAX4 and α-PALNRF-1 represent new therapeutic targets to inhibit proteolysis in catabolic diseases (e.g., type-2 diabetes, cancer).
| S-EPMC11104393 | biostudies-literature
Project description:Chromatin dynamics across cellular differentiation states is an emerging perspective from which the mechanism of global gene expression regulation may be better understood. While the roles of some histone marks have been partially interpreted in terms of their association with gene transcription, the dynamics of histone marks from a loci-specific perspective during cellular differentiation is not well studied. We established a method to systematically assess the histone modification variations of genes across various cellular differentiation states. We calculated the histone modification variation scores of H3K4me3, H3K27me3 and H3K36me3 for over 1300 curated transcription factors (TFs) during human blood cell differentiation. Hematopoietic-specific TFs (identified by literature mining) were significantly overrepresented by TFs with higher histone modification variation scores. Hierarchical clustering of all TFs based on the histone modification variation scores defined a group of TFs where known or potential hematopoietic-specific TFs were remarkably enriched. Our results suggest that local chromatin state dynamics of transcription factors across cellular differentiation states could imply cell lineage-specific functions. More importantly, our method can be applied to broader systems, holding the promise to discover de novo, lineage-specific TFs by interrogating their histone modification dynamics across cell lineages.
| S-EPMC3329503 | biostudies-literature