scholarly journals A Panel of rSNPs Demonstrating Allelic Asymmetry in Both ChIP-seq and RNA-seq Data and the Search for Their Phenotypic Outcomes through Analysis of DEGs

2021 ◽  
Vol 22 (14) ◽  
pp. 7240
Author(s):  
Elena E. Korbolina ◽  
Leonid O. Bryzgalov ◽  
Diana Z. Ustrokhanova ◽  
Sergey N. Postovalov ◽  
Dmitry V. Poverin ◽  
...  

Currently, the detection of the allele asymmetry of gene expression from RNA-seq data or the transcription factor binding from ChIP-seq data is one of the approaches used to identify the functional genetic variants that can affect gene expression (regulatory SNPs or rSNPs). In this study, we searched for rSNPs using the data for human pulmonary arterial endothelial cells (PAECs) available from the Sequence Read Archive (SRA). Allele-asymmetric binding and expression events are analyzed in paired ChIP-seq data for H3K4me3 mark and RNA-seq data obtained for 19 individuals. Two statistical approaches, weighted z-scores and predicted probabilities, were used to improve the efficiency of finding rSNPs. In total, we identified 14,266 rSNPs associated with both allele-specific binding and expression. Among them, 645 rSNPs were associated with GWAS phenotypes; 4746 rSNPs were reported as eQTLs by GTEx, and 11,536 rSNPs were located in 374 candidate transcription factor binding motifs. Additionally, we searched for the rSNPs associated with gene expression using an SRA RNA-seq dataset for 281 clinically annotated human postmortem brain samples and detected eQTLs for 2505 rSNPs. Based on these results, we conducted Gene Ontology (GO), Disease Ontology (DO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and constructed the protein–protein interaction networks to represent the top-ranked biological processes with a possible contribution to the phenotypic outcome.

2014 ◽  
Vol 42 (15) ◽  
pp. 9753-9760 ◽  
Author(s):  
Cai Chen ◽  
Ralf Bundschuh

Abstract Binding of transcription factors to their binding sites in promoter regions is the fundamental event in transcriptional gene regulation. When a transcription factor binding site is located within a nucleosome, the DNA has to partially unwrap from the nucleosome to allow transcription factor binding. This reduces the rate of transcription factor binding and is a known mechanism for regulation of gene expression via chromatin structure. Recently a second mechanism has been reported where transcription factor off-rates are dramatically increased when binding to target sites within the nucleosome. There are two possible explanations for such an increase in off-rate short of an active role of the nucleosome in pushing the transcription factor off the DNA: (i) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (ii) the nucleosome can change the equilibrium between specific and non-specific binding to the DNA. We explicitly model both scenarios and find that dimeric binding can explain a large increase in off-rate while the non-specific binding model cannot be reconciled with the large, experimentally observed increase. Our results suggest a general mechanism how nucleosomes increase transcription factor dissociation to promote exchange of transcription factors and regulate gene expression.


Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 446 ◽  
Author(s):  
Shijie Xin ◽  
Xiaohui Wang ◽  
Guojun Dai ◽  
Jingjing Zhang ◽  
Tingting An ◽  
...  

The proinflammatory cytokine, interleukin-6 (IL-6), plays a critical role in many chronic inflammatory diseases, particularly inflammatory bowel disease. To investigate the regulation of IL-6 gene expression at the molecular level, genomic DNA sequencing of Jinghai yellow chickens (Gallus gallus) was performed to detect single-nucleotide polymorphisms (SNPs) in the region −2200 base pairs (bp) upstream to 500 bp downstream of IL-6. Transcription factor binding sites and CpG islands in the IL-6 promoter region were predicted using bioinformatics software. Twenty-eight SNP sites were identified in IL-6. Four of these 28 SNPs, three [−357 (G > A), −447 (C > G), and −663 (A > G)] in the 5′ regulatory region and one in the 3′ non-coding region [3177 (C > T)] are not labelled in GenBank. Bioinformatics analysis revealed 11 SNPs within the promoter region that altered putative transcription factor binding sites. Furthermore, the C-939G mutation in the promoter region may change the number of CpG islands, and SNPs in the 5′ regulatory region may influence IL-6 gene expression by altering transcription factor binding or CpG methylation status. Genetic diversity analysis revealed that the newly discovered A-663G site significantly deviated from Hardy-Weinberg equilibrium. These results provide a basis for further exploration of the promoter function of the IL-6 gene and the relationships of these SNPs to intestinal inflammation resistance in chickens.


2016 ◽  
Vol 39 (5) ◽  
pp. 435-447 ◽  
Author(s):  
Meixiang Xu ◽  
Courtney E. Cross ◽  
Jordan T. Speidel ◽  
Sherif Z. Abdel-Rahman

2012 ◽  
Vol 29 (4) ◽  
pp. 468-475 ◽  
Author(s):  
Rosario M. Piro ◽  
Ivan Molineris ◽  
Ferdinando Di Cunto ◽  
Roland Eils ◽  
Rainer König

PLoS Genetics ◽  
2013 ◽  
Vol 9 (9) ◽  
pp. e1003748 ◽  
Author(s):  
Mathilde Paris ◽  
Tommy Kaplan ◽  
Xiao Yong Li ◽  
Jacqueline E. Villalta ◽  
Susan E. Lott ◽  
...  

PLoS Genetics ◽  
2014 ◽  
Vol 10 (9) ◽  
pp. e1004663 ◽  
Author(s):  
Nicholas E. Banovich ◽  
Xun Lan ◽  
Graham McVicker ◽  
Bryce van de Geijn ◽  
Jacob F. Degner ◽  
...  

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