Hidden heterogeneity of transcription factor binding sites: A case study of SF-1

Levitsky, Victor G.; Oshchepkov, Dmitry; Климова, Н. В.; Ignatieva, E. V.; Vasiliev, Gennady V.; Меркулов, В. М.; Меркулова, Т. И.

doi:10.1016/j.compbiolchem.2016.04.008

Cited by 7 publications

(8 citation statements)

References 76 publications

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“…physiological, pathological or adaptive) [ 20 – 22 ]. The benefits of GO term enrichment analysis for functional characterization of gene sets have been demonstrated in our previous publications [ 23 – 26 ].…”

Section: Methodsmentioning

confidence: 99%

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

2017

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BackgroundMany mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals.ResultsAfter a search for publications containing keywords: “whole genome”, “transcriptome or exome sequencing data”, and “genome-wide genotyping array data” authors looked for information related to genetic signatures ascribable to positive selection in Arctic or Antarctic mammalian species. Publications related to Human, Arctic fox, Yakut horse, Mammoth, Polar bear, and Minke whale were chosen. The compendium of genes that potentially underwent positive selection in >1 of these six species consisted of 416 genes. Twelve of them showed traces of positive selection in three species. Gene ontology term enrichment analysis of 416 genes from the compendium has revealed 13 terms relevant to the scope of this study. We found that enriched terms were relevant to three major groups: terms associated with collagen proteins and the extracellular matrix; terms associated with the anatomy and physiology of cilium; terms associated with docking. We further revealed that genes from compendium were over-represented in the lists of genes expressed in the lung and liver.ConclusionsA compendium combining mammalian genes involved in adaptation to cold environment was designed, based on the intersection of positively selected genes from six Arctic and Antarctic species. The compendium contained 416 genes that have been positively selected in at least two species. However, we did not reveal any positively selected genes that would be related to cold adaptation in all species from our list. But, our work points to several strong candidate genes involved in mechanisms and biochemical pathways related to cold adaptation response in different species.Electronic supplementary materialThe online version of this article (10.1186/s12863-017-0580-9) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

2017

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“…The computer methods for recognition of TFBSs in DNA sequences are free of this disadvantage but yet ineffective in detection of both TFBSs and the SNPs changing these sites without the cooperation with omics experiments. The objective reasons here are a high degeneracy of the regulatory DNA code [ 15 , 109 , 181 , 182 ]; high importance of low-affinity sites in gene regulation [ 183 ]; the presence of structural variants of the binding sites for the same TF [ 184 , 185 , 186 , 187 ]; and even nonconsensus TFBSs [ 188 , 189 ]. All these facts considerably decrease the efficacy of the available methods for TFBS recognition, most of which are based on the PWM model, which oversimplifies the mechanisms underlying TF–DNA interaction [ 66 , 68 , 69 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

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

Degtyareva

Antontseva

Merkulova

2021

IJMS

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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.

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“…The benefits of using the ontological and pathway analyses for functional annotation of group of genes revealed by different criteria have been considered in numerous publications [38, 61, 62]…”

Section: Discussionmentioning

confidence: 99%

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

et al. 2016

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BackgroundObesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation.ResultsThe compendium of genes controlling FB or BW includes 578 human genes. Candidate genes were identified from various sources, including previously published original research and review articles, GWAS meta-analyses, and OMIM (Online Mendelian Inheritance in Man). All genes were ranked according to knowledge about their biological role in body weight regulation and classified according to expression patterns or functional characteristics. Substantial and overrepresented numbers of genes from the compendium encoded cell surface receptors, signaling molecules (hormones, neuropeptides, cytokines), transcription factors, signal transduction proteins, cilium and BBSome components, and lipid binding proteins or were present in the brain-specific list of tissue-enriched genes identified with TSEA tool. We identified 27 pathways from KEGG, REACTOME and BIOCARTA whose genes were overrepresented in the compendium. Networks formed by physical interactions or homological relationships between proteins or interactions between proteins involved in biochemical/signaling pathways were reconstructed and analyzed. Subnetworks and clusters identified by the MCODE tool included genes/proteins associated with cilium morphogenesis, signal transduction proteins (particularly, G protein–coupled receptors, kinases or proteins involved in response to insulin stimulus) and transcription regulation (particularly nuclear receptors). We ranked GWAS genes according to the number of neighbors in three networks and revealed 22 GWAS genes involved in the brain-specific PPI network. On the base of the most reliable PPIs functioning in the brain tissue, new regulatory schemes interpreting relevance to BW regulation are proposed for three GWAS genes (ETV5, LRP1B, and NDUFS3). ConclusionsA compendium comprising 578 human genes controlling FB or BW was designed, and the most significant functional groups of genes, biological processes/pathways, and tissues/organs involved in BW regulation were revealed. We ranked genes from the GWAS meta-analysis set according to the number and quality of associations in the networks and then according to their involvement in the brain-specific PPI network and proposed new regulatory schemes involving three GWAS genes (ETV5, LRP1B, and NDUFS3) in BW regulation. The compendium is expected to be useful for pathology risk estimation and for design of new pharmacological approaches in the treatment of human obesity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0466-2) contains supplementary material, which is available to authorized users.

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Hidden heterogeneity of transcription factor binding sites: A case study of SF-1

Cited by 7 publications

References 76 publications

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

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

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

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