Transcription factors (TFs) recognize specific bases within their DNA-binding motifs, with each base contributing nearly independently to total binding energy. However, the energetic contributions of particular dinucleotides can deviate strongly from the additive approximation, indicating that some TFs can specifically recognize DNA dinucleotides. Here we solved high-resolution (<1 Å) structures of MYF5 and BARHL2 bound to DNAs containing sets of dinucleotides that have different affinities to the proteins.
View Article and Find Full Text PDFBackground: Occupational health factors such as shift work, sleep, fatigue, and work environment jeopardise the health and safety of gas station workers. This calls for new research to investigate how the working environment and characteristics impact the occupational health of workers at gas stations. However, minimal research has been conducted in this field, especially those involving psychological and behavioural factors, occupational stress, and so forth.
View Article and Find Full Text PDFThe interplay between histone modifications and DNA methylation drives the establishment and maintenance of the cellular epigenomic landscape, but it remains challenging to investigate the complex relationship between these epigenetic marks across the genome. Here we describe a nanopore-sequencing-based-method, nanoHiMe-seq, for interrogating the genome-wide localization of histone modifications and DNA methylation from single DNA molecules. nanoHiMe-seq leverages a nonspecific methyltransferase to exogenously label adenine bases proximal to antibody-targeted modified nucleosomes in situ.
View Article and Find Full Text PDFFront Immunol
October 2022
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disease in the central nervous system (CNS). Its pathogenesis is quite complex: Accumulated evidence suggests that biochemical signals as well as mechanical stimuli play important roles in MS. In both patients and animal models of MS, brain viscoelasticity is reduced during disease progression.
View Article and Find Full Text PDFSelective catalytic reduction of nitrogen oxides (NO ) with C H (C H -SCR) was investigated over NiO catalysts supported on different metal-oxides. A NiAlO mixed oxide phase was formed over NiO/γ-Al O catalyst, inducing an immediate interaction between NiO and AlO species. Such interaction resulted in a charge transfer from Ni to Al site and the formation of Ni species in high oxidation state.
View Article and Find Full Text PDFOptical fiber sensing technology plays an important role in the application of the sensing layer of the Internet of Things. The core of this technology is the demodulation of the fiber Bragg grating (FBG) sensing system. Since the FBG sensor utilizes the wavelength change to respond to the measured size, it is of great significance to improve the accuracy of the FBG wavelength demodulation.
View Article and Find Full Text PDFMany sequence variants have been linked to complex human traits and diseases, but deciphering their biological functions remains challenging, as most of them reside in noncoding DNA. Here we have systematically assessed the binding of 270 human transcription factors to 95,886 noncoding variants in the human genome using an ultra-high-throughput multiplex protein-DNA binding assay, termed single-nucleotide polymorphism evaluation by systematic evolution of ligands by exponential enrichment (SNP-SELEX). The resulting 828 million measurements of transcription factor-DNA interactions enable estimation of the relative affinity of these transcription factors to each variant in vitro and evaluation of the current methods to predict the effects of noncoding variants on transcription factor binding.
View Article and Find Full Text PDFPseudomonas syringae is a Gram-negative and model pathogenic bacterium that causes plant diseases worldwide. Here, we set out to identify binding motifs for all 301 annotated transcription factors (TFs) of P. syringae using HT-SELEX.
View Article and Find Full Text PDFRNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation, and stability. Despite their central role in RNA function, the RNA-binding specificities of most RBPs remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA-binding domains (RBDs) and assessed their specificities using high-throughput RNA-SELEX (HTR-SELEX).
View Article and Find Full Text PDFNucleosomes cover most of the genome and are thought to be displaced by transcription factors in regions that direct gene expression. However, the modes of interaction between transcription factors and nucleosomal DNA remain largely unknown. Here we systematically explore interactions between the nucleosome and 220 transcription factors representing diverse structural families.
View Article and Find Full Text PDFPM samples were collected from 45 sites around the electroplating factories in five towns in Dongguan at different times during all four seasons in 2015. The contents of 12 heavy metals (HMs) from the PM samples were analyzed by ICP-MS. The seasonal and spatial distribution characteristics and the ecological risk were analyzed to provide a scientific foundation for the relevant department to make decisions regarding the environmental hazard, risk assessment and, pollution control.
View Article and Find Full Text PDFThis study selected Guiyu Town, Guangdong Province as the research area, the content of 15 kinds of metals (As, Be, Cd, Co, Cr, Cu, Hg, Li, Mn, Ni, Sb, Sn, Pb, V, and Zn) in the soil was determined, and the content of heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the rice of this research area was identified. Multivariate statistical analysis and a human health risk assessment model were used to investigate the distribution characteristics and health risk of heavy metals in a soil-rice system. The results showed that Hg, Sb, and Sn in the surface soil surrounding the electronic waste dismantling area have obvious accumulation effect.
View Article and Find Full Text PDFMost transcription factors (TFs) can bind to a population of sequences closely related to a single optimal site. However, some TFs can bind to two distinct sequences that represent two local optima in the Gibbs free energy of binding (ΔG). To determine the molecular mechanism behind this effect, we solved the structures of human HOXB13 and CDX2 bound to their two optimal DNA sequences, CAATAAA and TCGTAAA.
View Article and Find Full Text PDFTranscription factors (TFs) recognize specific DNA sequences to control chromatin and transcription, forming a complex system that guides expression of the genome. Despite keen interest in understanding how TFs control gene expression, it remains challenging to determine how the precise genomic binding sites of TFs are specified and how TF binding ultimately relates to regulation of transcription. This review considers how TFs are identified and functionally characterized, principally through the lens of a catalog of over 1,600 likely human TFs and binding motifs for two-thirds of them.
View Article and Find Full Text PDFIn some dimeric cases of transcription factor (TF) binding, the specificity of dimeric motifs has been observed to differ notably from what would be expected were the two factors to bind to DNA independently of each other. Current motif discovery methods are unable to learn monomeric and dimeric motifs in modular fashion such that deviations from the expected motif would become explicit and the noise from dimeric occurrences would not corrupt monomeric models. We propose a novel modeling technique and an expectation maximization algorithm, implemented as software tool MODER, for discovering monomeric TF binding motifs and their dimeric combinations.
View Article and Find Full Text PDFThe majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences.
View Article and Find Full Text PDFTo investigate the distribution characteristics and the human health risks of heavy metals in surface water samples, 30 samples were collected around electroplating factories of Machong, Shatian, Humen, Changan and Dalingshan towns in Dongguan city, 8 heavy metals(As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) contents were measured and analyzed by using multivariate statistical analysis method and human health risk assessment model. The results showed that the maximum concentrations of Cr, Pb and the average concentration of Hg exceeded Environmental Quality Standards for Surface Water(GB 3838-2002, Grade Ⅲ), the concentrations of Cr, Cu, Hg, Ni, Zn and Pb during rainy season were all higher than that those during dry season. Multivariate statistical analysis indicated that Cd, Cr, Cu, Ni and Zn mainly originated from the contaminated electroplating factories, Pb and Hg were mainly affected by the traffic sources, and As was significantly correlated with natural sources.
View Article and Find Full Text PDFTranscription factors (TFs) achieve DNA-binding specificity through contacts with functional groups of bases (base readout) and readout of structural properties of the double helix (shape readout). Currently, it remains unclear whether DNA shape readout is utilized by only a few selected TF families, or whether this mechanism is used extensively by most TF families. We resequenced data from previously published HT-SELEX experiments, the most extensive mammalian TF-DNA binding data available to date.
View Article and Find Full Text PDFC2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined.
View Article and Find Full Text PDFThe mammalian cell cycle is controlled by the E2F family of transcription factors. Typical E2Fs bind to DNA as heterodimers with the related dimerization partner (DP) proteins, whereas the atypical E2Fs, E2F7 and E2F8 contain two DNA-binding domains (DBDs) and act as repressors. To understand the mechanism of repression, we have resolved the structure of E2F8 in complex with DNA at atomic resolution.
View Article and Find Full Text PDFGene expression is regulated by transcription factors (TFs), proteins that recognize short DNA sequence motifs. Such sequences are very common in the human genome, and an important determinant of the specificity of gene expression is the cooperative binding of multiple TFs to closely located motifs. However, interactions between DNA-bound TFs have not been systematically characterized.
View Article and Find Full Text PDFDivergent morphology of species has largely been ascribed to genetic differences in the tissue-specific expression of proteins, which could be achieved by divergence in cis-regulatory elements or by altering the binding specificity of transcription factors (TFs). The relative importance of the latter has been difficult to assess, as previous systematic analyses of TF binding specificity have been performed using different methods in different species. To address this, we determined the binding specificities of 242 Drosophila TFs, and compared them to human and mouse data.
View Article and Find Full Text PDFIt has been recently ascribed to several inflammatory cytokines (i.e. TGF-β3, TNF-α, and IL-1) a functional role in regulating Sertoli cell blood-testis barrier (BTB) dynamics.
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