scholarly journals Gene Expression and Regulatory Webwork of POLR2K in Bladder Carcinogenesis by Integrated Bioinformatics Approaches

2020 ◽  
Author(s):  
Liliang Yang ◽  
Kaizhen Wang ◽  
Wenjing Guo ◽  
Xian Chen ◽  
Qinglong Guo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transcription Factor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Transcription Factor Binding ◽  
Sequencing Data ◽  
Factor Binding

Abstract Background：RNA polymerase II subunit K (POLR2K) belongs to one of the multiple subunits of RNA polymerase II (Pol II), whose biological function is to synthesize mRNA. Aberrant POLR2K expression is related to carcinogenesis. However, POLR2K’s underlying role in bladder cancer has not been explored. In the current study, we intend to analyze the function of POLR2K and its regulatory network within bladder cancer.Methods: Public sequencing data was obtained from GEO and TCGA to investigate POLR2K expression and regulatory network within bladder cancer (BLCA) by using GEPIA and Oncomine as well as cBioPortal online tool. LinkedOmics was employed to identify genes displaying significantly differential expression patterns and to perform GO and KEGG analyses. After differential genes was assigned and ranked, GSEA analyses was performed to obtain target networks for transcription factors, miRNAs, and kinases that could regulate POLR2K–associated gene network. Subsequent functional webwork analyses were used to identify cancer-relevant pathways Moreover, POLR2K gene is verified, by ChIP-seq in MCF-7 cell line , with transcription factor binding evidence in the ENCODE Transcription Factor Binding Site Profiles dataset.Conclusions: The current study implies that POLR2K gene is overexpressed and often amplified in BLCA, providing the first evidence that POLR2K deregulation, in particular increased transcription, may promote BLCA. These findings uncover a unique expression patterns of POLR2K and its potential regulatory networks in BLCA, contributing greatly to study of the role of POLR2K in cancer development.

scholarly journals Gene Expression and Regulatory Webwork of POLR2K in Bladder Carcinogenesis by Integrated Bioinformatics Approaches

2020 ◽  
Author(s):  
Liliang Yang ◽  
Kaizhen Wang ◽  
Wenjing Guo ◽  
Xian Chen ◽  
Qinglong Guo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transcription Factor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Regulatory Network ◽  
Expression Patterns ◽  
Transcription Factor Binding ◽  
Biological Behavior ◽  
G1 Arrest ◽  
Factor Binding

Abstract Background：RNA polymerase II subunit K (POLR2K) belongs to one of the multiple subunits of RNA polymerase II (Pol II), whose biological function is to synthesize mRNA. Aberrant POLR2K expression is related to carcinogenesis. However, POLR2K’s underlying role in bladder cancer has not been explored. In the current study, we intend to analyze the function of POLR2K and its regulatory network within bladder cancer.Methods: Public sequencing data was obtained from GEO and TCGA to investigate POLR2K expression and regulatory network within bladder cancer (BLCA) by using GEPIA and Oncomine as well as cBioPortal online tool. LinkedOmics was employed to identify genes displaying significantly differential expression patterns and to perform GO and KEGG analyses. After differential genes was assigned and ranked, GSEA analysis was performed to obtain target networks for transcription factors, miRNAs, and kinases that could regulate POLR2K–associated gene network. Subsequent functional webwork analyses were used to identify cancer-relevant pathways Moreover, POLR2K gene is verified by ChIP-seq in MCF-7 cell line with transcription factor binding evidence in the ENCODE Transcription Factor Binding Site Profiles dataset. In the end, the biological behavior of POLR2K in BLCA was validated by cell function experiments and tissue micro-assay.Conclusions: The current study implies that POLR2K gene is overexpressed and often amplified in BLCA, providing the first evidence that POLR2K deregulation, especially increased transcription, may promote BLCA. Knocking down POLR2K in BLCA 5637 and T24 cells could decrease cellular viability, reduce metastasis ability and induce G1 arrest, which might be mediated by E2F1. These findings uncover a unique expression pattern of POLR2K and its potential regulatory networks in BLCA, contributing greatly to study of the role of POLR2K in cancer development.

scholarly journals Constructing gene regulatory networks using epigenetic data

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Abhijeet Rajendra Sonawane ◽  
Dawn L. DeMeo ◽  
John Quackenbush ◽  
Kimberly Glass
Keyword(s):  
Transcription Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Message Passing ◽  
Regulatory Networks ◽  
Transcription Factor Binding ◽  
Network Reconstruction ◽  
Sequence Motif ◽  
Factor Binding ◽  
Gene Regulatory

AbstractThe biological processes that drive cellular function can be represented by a complex network of interactions between regulators (transcription factors) and their targets (genes). A cell’s epigenetic state plays an important role in mediating these interactions, primarily by influencing chromatin accessibility. However, how to effectively use epigenetic data when constructing a gene regulatory network remains an open question. Almost all existing network reconstruction approaches focus on estimating transcription factor to gene connections using transcriptomic data. In contrast, computational approaches for analyzing epigenetic data generally focus on improving transcription factor binding site predictions rather than deducing regulatory network relationships. We bridged this gap by developing SPIDER, a network reconstruction approach that incorporates epigenetic data into a message-passing framework to estimate gene regulatory networks. We validated SPIDER’s predictions using ChIP-seq data from ENCODE and found that SPIDER networks are both highly accurate and include cell-line-specific regulatory interactions. Notably, SPIDER can recover ChIP-seq verified transcription factor binding events in the regulatory regions of genes that do not have a corresponding sequence motif. The networks estimated by SPIDER have the potential to identify novel hypotheses that will allow us to better characterize cell-type and phenotype specific regulatory mechanisms.

scholarly journals Subtype-associated epigenomic landscape and 3D genome structure in bladder cancer

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tejaswi Iyyanki ◽  
Baozhen Zhang ◽  
Qixuan Wang ◽  
Ye Hou ◽  
Qiushi Jin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transcription Factor ◽  
Cancer Cell ◽  
Genome Structure ◽  
Transcription Factor Binding ◽  
Specific Gene ◽  
Open Chromatin ◽  
Factor Binding ◽  
3D Genome ◽  
Genome Wide

Abstract Muscle-invasive bladder cancers are characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. Transcriptionally, FOXA1, GATA3, and PPARG are shown to be essential for luminal subtype-specific gene regulation and subtype switching, while TP63, STAT3, and TFAP2 family members are critical for regulation of basal subtype-specific genes. Despite these advances, the underlying epigenetic mechanisms and 3D chromatin architecture responsible for subtype-specific regulation in bladder cancer remain unknown. Result We determine the genome-wide transcriptome, enhancer landscape, and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer. Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration. Conclusion In summary, our work identifies unique epigenomic signatures and 3D genome structures in luminal and basal urinary bladder cancers and suggests a novel link between the circadian transcription factor NPAS2 and a clinical bladder cancer subtype.

scholarly journals Methods of MicroRNA Promoter Prediction and Transcription Factor Mediated Regulatory Network

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yuming Zhao ◽  
Fang Wang ◽  
Su Chen ◽  
Jun Wan ◽  
Guohua Wang
Keyword(s):  
Transcription Factor ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
High Throughput Sequencing ◽  
Prediction Models ◽  
Promoter Prediction ◽  
Sequencing Data ◽  
Protein Coding ◽  
Mirna Genes ◽  
Intergenic Regions

MicroRNAs (miRNAs) are short (~22 nucleotides) noncoding RNAs and disseminated throughout the genome, either in the intergenic regions or in the intronic sequences of protein-coding genes. MiRNAs have been proved to play important roles in regulating gene expression. Hence, understanding the transcriptional mechanism of miRNA genes is a very critical step to uncover the whole regulatory network. A number of miRNA promoter prediction models have been proposed in the past decade. This review summarized several most popular miRNA promoter prediction models which used genome sequence features, or other features, for example, histone markers, RNA Pol II binding sites, and nucleosome-free regions, achieved by high-throughput sequencing data. Some databases were described as resources for miRNA promoter information. We then performed comprehensive discussion on prediction and identification of transcription factor mediated microRNA regulatory networks.

scholarly journals Discovering unknown human and mouse transcription factor binding sites and their characteristics from ChIP-seq data

2021 ◽  
Vol 118 (20) ◽  
pp. e2026754118
Author(s):  
Chun-Ping Yu ◽  
Chen-Hao Kuo ◽  
Chase W. Nelson ◽  
Chi-An Chen ◽  
Zhi Thong Soh ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Sequencing Data ◽  
Transcription Start Sites ◽  
Factor Binding ◽  
Quality Control Criterion ◽  
Intergenic Regions ◽  
Human And Mouse

Transcription factor binding sites (TFBSs) are essential for gene regulation, but the number of known TFBSs remains limited. We aimed to discover and characterize unknown TFBSs by developing a computational pipeline for analyzing ChIP-seq (chromatin immunoprecipitation followed by sequencing) data. Applying it to the latest ENCODE ChIP-seq data for human and mouse, we found that using the irreproducible discovery rate as a quality-control criterion resulted in many experiments being unnecessarily discarded. By contrast, the number of motif occurrences in ChIP-seq peak regions provides a highly effective criterion, which is reliable even if supported by only one experimental replicate. In total, we obtained 2,058 motifs from 1,089 experiments for 354 human TFs and 163 motifs from 101 experiments for 34 mouse TFs. Among these motifs, 487 have not previously been reported. Mapping the canonical motifs to the human genome reveals a high TFBS density ±2 kb around transcription start sites (TSSs) with a peak at −50 bp. On average, a promoter contains 5.7 TFBSs. However, 70% of TFBSs are in introns (41%) and intergenic regions (29%), whereas only 12% are in promoters (−1 kb to +100 bp from TSSs). Notably, some TFs (e.g., CTCF, JUN, JUNB, and NFE2) have motifs enriched in intergenic regions, including enhancers. We inferred 142 cobinding TF pairs and 186 (including 115 completely) tethered binding TF pairs, indicating frequent interactions between TFs and a higher frequency of tethered binding than cobinding. This study provides a large number of previously undocumented motifs and insights into the biological and genomic features of TFBSs.

scholarly journals Inference of tumor cell-specific transcription factor binding from cell-free DNA enables tumor subtype prediction and early detection of cancer

2018 ◽  
Author(s):  
Peter Ulz ◽  
Samantha Perakis ◽  
Qing Zhou ◽  
Tina Moser ◽  
Jelena Belic ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Early Detection ◽  
Transcription Factor Binding ◽  
Patient Specific ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Cell Free Dna ◽  
Specific Transcription Factor ◽  
Factor Binding ◽  
Free Dna

AbstractDeregulation of transcription factors (TFs) is an important driver of tumorigenesis. We developed and validated a minimally invasive method for assessing TF activity based on cell-free DNA sequencing and nucleosome footprint analysis. We analyzed whole genome sequencing data for >1,000 cell-free DNA samples from cancer patients and healthy controls using a newly developed bioinformatics pipeline that infers accessibility of TF binding sites from cell-free DNA fragmentation patterns. We observed patient-specific as well as tumor-specific patterns, including accurate prediction of tumor subtypes in prostate cancer, with important clinical implications for the management of patients. Furthermore, we show that cell-free DNA TF profiling is capable of early detection of colorectal carcinomas. Our approach for mapping tumor-specific transcription factor bindingin vivobased on blood samples makes a key part of the noncoding genome amenable to clinical analysis.

scholarly journals A Mutation in the Drosophila melanogaster eve Stripe 2 Minimal Enhancer Is Buffered by Flanking Sequences

2020 ◽  
Vol 10 (12) ◽  
pp. 4473-4482
Author(s):  
Francheska López-Rivera ◽  
Olivia K. Foster Rhoades ◽  
Ben J. Vincent ◽  
Edward C. G. Pym ◽  
Meghan D. J. Bragdon ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Binding Site ◽  
Expression Pattern ◽  
Dna Sequences ◽  
Expression Patterns ◽  
Transcription Factor Binding ◽  
Genomic Context ◽  
Site Mutation ◽  
Factor Binding

Enhancers are DNA sequences composed of transcription factor binding sites that drive complex patterns of gene expression in space and time. Until recently, studying enhancers in their genomic context was technically challenging. Therefore, minimal enhancers, the shortest pieces of DNA that can drive an expression pattern that resembles a gene’s endogenous pattern, are often used to study features of enhancer function. However, evidence suggests that some enhancers require sequences outside the minimal enhancer to maintain function under environmental perturbations. We hypothesized that these additional sequences also prevent misexpression caused by a transcription factor binding site mutation within a minimal enhancer. Using the Drosophila melanogaster even-skipped stripe 2 enhancer as a case study, we tested the effect of a Giant binding site mutation (gt-2) on the expression patterns driven by minimal and extended enhancer reporter constructs. We found that, in contrast to the misexpression caused by the gt-2 binding site deletion in the minimal enhancer, the same gt-2 binding site deletion in the extended enhancer did not have an effect on expression. The buffering of expression levels, but not expression pattern, is partially explained by an additional Giant binding site outside the minimal enhancer. Deleting the gt-2 binding site in the endogenous locus had no significant effect on stripe 2 expression. Our results indicate that rules derived from mutating enhancer reporter constructs may not represent what occurs in the endogenous context.

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