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 Subtype-specific epigenomic landscape and 3D genome structure in bladder cancer

2020 ◽  
Author(s):  
Tejaswi Iyyanki ◽  
Baozhen Zhang ◽  
Qiushi Jin ◽  
Hongbo Yang ◽  
Tingting Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cell ◽  
Genome Structure ◽  
Epigenetic Mechanism ◽  
Open Chromatin ◽  
3D Genome ◽  
Genome Wide ◽  
Specific Regulation ◽  
And Migration ◽  
3D Genome Structure

AbstractMuscle-invasive bladder cancers have recently been 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. For example, FOXA1, GATA3, and PPARG have been shown to be essential for luminal subtype-specific regulation and subtype switching, while TP63 and STAT3 are critical for basal subtype bladder cancer. Despite these advances, the underlying epigenetic mechanism and 3D chromatin architecture for subtype-specific regulation in bladder cancers remains largely unknown. Here, we determined the genome-wide transcriptome, enhancer landscape, TF binding profiles (FOXA1 and GATA3) in luminal and basal subtypes of bladder cancers. Furthermore, we mapped genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors, for the first time in bladder cancer. We showed that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct TF binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identified a novel clinically relevant transcriptional factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other luminal-specific genes (such as FOXA1, GATA3, and PPARG) and affects cancer cell proliferation and migration. In summary, our work shows a subtype-specific epigenomic and 3D genome structure in urinary bladder cancers and suggested a novel link between the circadian TF NPAS2 and a clinical bladder cancer subtype.

scholarly journals Genome-wide transcription factor binding in leaves from C3 and C4 grasses

2017 ◽  
Author(s):  
Steven J. Burgess ◽  
Ivan Reyna-Llorens ◽  
Sean R. Stevenson ◽  
Pallavi Singh ◽  
Katja Jaeger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Brachypodium Distachyon ◽  
Transcription Factor Binding ◽  
Bundle Sheath ◽  
Individual Species ◽  
Specific Gene ◽  
Factor Binding ◽  
Genome Wide ◽  
Photosynthesis Gene

AbstractThe majority of plants use C3 photosynthesis, but over sixty independent lineages of angiosperms have evolved the C4 pathway. In most C4 species, photosynthesis gene expression is compartmented between mesophyll and bundle sheath cells. We performed DNaseI-SEQ to identify genome-wide profiles of transcription factor binding in leaves of the C4 grasses Zea mays, Sorghum bicolor and Setaria italica as well as C3Brachypodium distachyon. In C4 species, while bundle sheath strands and whole leaves shared similarity in the broad regions of DNA accessible to transcription factors, the short sequences bound varied. Transcription factor binding was prevalent in gene bodies as well as promoters, and many of these sites could represent duons that impact gene regulation in addition to amino acid sequence. Although globally there was little correlation between any individual DNaseI footprint and cell-specific gene expression, within individual species transcription factor binding to the same motifs in multiple genes provided evidence for shared mechanisms governing C4 photosynthesis gene expression. Furthermore, interspecific comparisons identified a small number of highly conserved transcription factor binding sites associated with leaves from species that diverged around 60 million years ago. These data therefore provide insight into the architecture associated with C4 photosynthesis gene expression in particular and characteristics of transcription factor binding in cereal crops in general.One sentence summaryGenome-wide patterns of transcription factor binding in vivo defined by DNaseI for leaves of C3 and C4 grasses

scholarly journals ATAC-seq Data for Genome-Wide Profiling of Transcription Factor Binding Sites in the Rice False Smut Fungus Ustilaginoidea virens

2021 ◽  
Author(s):  
Xiaoyang Chen ◽  
Hao Liu ◽  
Xiao-Lin Chen ◽  
Junbin Huang ◽  
Tom Hsiang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Smut Fungus ◽  
Open Chromatin ◽  
Ustilaginoidea Virens ◽  
Factor Binding ◽  
Genome Wide ◽  
False Smut

Identification of transcription factor binding-sites is one of the most important steps in understanding the function of transcription factors and regulatory networks in organisms. The Assay for Transposase Accessible Chromatin Sequencing (ATAC-seq) is a simple protocol for detection of open chromatin, which could be a powerful tool to advance studies of protein:DNA interactions. Although ATAC-seq has been used in systematic identification of cis-regulatory regions in animal and plant genomes, this method has been rarely applied in fungi. Here, we describe a valuable ATAC-seq resource in the genome of an economically important phytopathogen, the rice false smut fungus, Ustilaginoidea virens. The ATAC-seq data of U. virens mycelia collected from potato sucrose broth (PSB) and PSB supplied with rice spikelet extract (RSE) were both generated. This is the first genome-wide profiling of open chromatin and transcription factor binding sites in U. virens.

scholarly journals Genome-Wide Identification of Transcription Start Sites, Promoters and Transcription Factor Binding Sites in E. coli

PLoS ONE ◽  
2009 ◽  
Vol 4 (10) ◽  
pp. e7526 ◽  
Author(s):  
Alfredo Mendoza-Vargas ◽  
Leticia Olvera ◽  
Maricela Olvera ◽  
Ricardo Grande ◽  
Leticia Vega-Alvarado ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Transcription Start ◽  
Transcription Start Sites ◽  
E Coli ◽  
Factor Binding ◽  
Genome Wide

scholarly journals Identification and characterization of constrained non-exonic bases lacking predictive epigenomic and transcription factor binding annotations

2019 ◽  
Author(s):  
Olivera Grujic ◽  
Tanya N. Phung ◽  
Soo Bin Kwon ◽  
Adriana Arneson ◽  
Yuju Lee ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factor Binding ◽  
Regulatory Sequence ◽  
Human Genetic Variation ◽  
Sequence Motifs ◽  
Variant Prioritization ◽  
Factor Binding ◽  
Genome Wide ◽  
Identification And Characterization

AbstractAnnotations of evolutionarily constraint provide important information for variant prioritization. Genome-wide maps of epigenomic marks and transcription factor binding provide complementary information for interpreting a subset of such prioritized variants. Here we developed the Constrained Non-Exonic Predictor (CNEP) to quantify the evidence of each base in the human genome being in a constrained non-exonic element from over 60,000 epigenomic and transcription factor binding features. We find that the CNEP score outperforms baseline and related existing scores at predicting constrained non-exonic bases from such data. However, a subset of such bases are still not well predicted by CNEP. We developed a complementary Conservation Signature Score by CNEP (CSS-CNEP) using conservation state and constrained element annotations that is predictive of those bases. Using human genetic variation, regulatory sequence motifs, mouse epigenomic data, and retrospectively considered additional human data we further characterize the nature of constrained non-exonic bases with low CNEP scores.

scholarly journals Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk

2018 ◽  
Vol 50 (10) ◽  
pp. 1483-1493 ◽  
Author(s):  
Yakir A. Reshef ◽  
Hilary K. Finucane ◽  
David R. Kelley ◽  
Alexander Gusev ◽  
Dylan Kotliar ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Disease Risk ◽  
Transcription Factor Binding ◽  
Factor Binding ◽  
Polygenic Disease ◽  
Genome Wide

scholarly journals Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1435
Author(s):  
Yu-Chin Lien ◽  
Paul Zhiping Wang ◽  
Xueqing Maggie Lu ◽  
Rebecca A. Simmons
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Transcription Factor Binding ◽  
Binding Motifs ◽  
Factor Binding ◽  
Intrauterine Growth ◽  
Gene Dysregulation ◽  
Genome Wide

Intrauterine growth retardation (IUGR), which induces epigenetic modifications and permanent changes in gene expression, has been associated with the development of type 2 diabetes. Using a rat model of IUGR, we performed ChIP-Seq to identify and map genome-wide histone modifications and gene dysregulation in islets from 2- and 10-week rats. IUGR induced significant changes in the enrichment of H3K4me3, H3K27me3, and H3K27Ac marks in both 2-wk and 10-wk islets, which were correlated with expression changes of multiple genes critical for islet function in IUGR islets. ChIP-Seq analysis showed that IUGR-induced histone mark changes were enriched at critical transcription factor binding motifs, such as C/EBPs, Ets1, Bcl6, Thrb, Ebf1, Sox9, and Mitf. These transcription factors were also identified as top upstream regulators in our previously published transcriptome study. In addition, our ChIP-seq data revealed more than 1000 potential bivalent genes as identified by enrichment of both H3K4me3 and H3K27me3. The poised state of many potential bivalent genes was altered by IUGR, particularly Acod1, Fgf21, Serpina11, Cdh16, Lrrc27, and Lrrc66, key islet genes. Collectively, our findings suggest alterations of histone modification in key transcription factors and genes that may contribute to long-term gene dysregulation and an abnormal islet phenotype in IUGR rats.

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