scholarly journals Dynamic Analysis of Gene Expression and Genome-wide Transcription Factor Binding during Lineage Specification of Multipotent Progenitors

2013 ◽  
Vol 13 (6) ◽  
pp. 754-768 ◽  
Author(s):  
Gillian May ◽  
Shamit Soneji ◽  
Alex J. Tipping ◽  
Jose Teles ◽  
Simon J. McGowan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Dynamic Analysis ◽  
Transcription Factor Binding ◽  
Lineage Specification ◽  
Factor Binding ◽  
Multipotent Progenitors ◽  
Genome Wide

scholarly journals Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases

2021 ◽  
Vol 22 (12) ◽  
pp. 6454
Author(s):  
Arina O. Degtyareva ◽  
Elena V. Antontseva ◽  
Tatiana I. Merkulova
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Genetic Variants ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Genome Wide Association Studies ◽  
Factor Binding ◽  
Genome Wide ◽  
Regulatory Snps

The vast majority of the genetic variants (mainly SNPs) associated with various human traits and diseases map to a noncoding part of the genome and are enriched in its regulatory compartment, suggesting that many causal variants may affect gene expression. The leading mechanism of action of these SNPs consists in the alterations in the transcription factor binding via creation or disruption of transcription factor binding sites (TFBSs) or some change in the affinity of these regulatory proteins to their cognate sites. In this review, we first focus on the history of the discovery of regulatory SNPs (rSNPs) and systematized description of the existing methodical approaches to their study. Then, we brief the recent comprehensive examples of rSNPs studied from the discovery of the changes in the TFBS sequence as a result of a nucleotide substitution to identification of its effect on the target gene expression and, eventually, to phenotype. We also describe state-of-the-art genome-wide approaches to identification of regulatory variants, including both making molecular sense of genome-wide association studies (GWAS) and the alternative approaches the primary goal of which is to determine the functionality of genetic variants. Among these approaches, special attention is paid to expression quantitative trait loci (eQTLs) analysis and the search for allele-specific events in RNA-seq (ASE events) as well as in ChIP-seq, DNase-seq, and ATAC-seq (ASB events) data.

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 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 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
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