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Runs of Homozygosity (ROH) regions are characterized by homozygous genotypes inherited from a common ancestor, often arising from positive selection for adaptive traits. These homozygous regions may arise due to inbreeding, selective breeding, or demographic events like population bottlenecks. Transcription factor binding sites (TFBS) are short, specific DNA sequences where transcription factors bind to regulate the expression of nearby genes. These sites are essential for controlling biological processes such as development, metabolism, and immune response. TFBS act as key regulatory elements, and their variations can influence gene activity, contributing to phenotypic differences and adaptation. ROH often encompass regulatory elements, including TFBS, suggesting a functional connection between these genomic features. This study investigates TFBS within ROH regions in 297 animals of six cattle breeds: Gir (48), Tharparkar (72), Vrindavani (72), Frieswal (14), Holstein Friesian (63), and Jersey (28). Utilizing genotyped data of these animals, we identified genomic regions enriched with ROH. We focused on the central 10 kb regions of 50 ROH regions common across all breeds. Within these regions, 450 motifs were examined, identifying 168 transcription factors potentially binding to these regions. The results emphasize the role of TFBS in gene regulation and adaptive processes. By linking ROH patterns to regulatory elements, this study enhances our understanding of the genetic architecture underlying phenotypic traits and their adaptation to environmental pressures. These findings provide insights into the molecular mechanisms influencing genetic variation in cattle populations.

A data set of promoter and 5′UTR sequences of homoeo‐alleles of 459 wheat genes that contribute to agriculturally important traits in 95 ancestral and commercial wheat cultivars is presented here. The high‐stringency myBaits technology used made individual capture of homoeo‐allele promoters possible, which is reported here for the first time. Promoters of most genes are remarkably conserved across the 83 hexaploid cultivars used with <7 haplotypes per promoter and 21% being identical to the reference Chinese Spring. InDels and many high‐confidence SNPs are located within predicted plant transcription factor binding sites, potentially changing gene expression. Most haplotypes found in the Watkins landraces and a few haplotypes found in Triticum monococcum, germplasms hitherto not thought to have been used in modern wheat breeding, are already found in many commercial hexaploid wheats. The full data set which is useful for genomic and gene function studies and wheat breeding is available at https://rrescloud.rothamsted.ac.uk/index.php/s/DMCFDu5iAGTl50u/authenticate.

Background We previously demonstrated that neuregulin-1 (NRG-1) was neuroprotective in rats following ischemic stroke. Neuroprotection by NRG-1 was associated with the suppression of pro-inflammatory gene expression in brain tissues. Over-activation of brain microglia can induce pro-inflammatory gene expression by activation of transcriptional regulators following stroke. Here, we examined how NRG-1 transcriptionally regulates inflammatory gene expression by computational bioinformatics and in vitro using microglial cells. Methods To identify transcriptional regulators involved in ischemia-induced inflammatory gene expression, rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO) and NRG-1 treatment. Gene expression profiles of brain tissues following ischemia and NRG-1 treatment were examined by microarray technology. The Conserved Transcription Factor-Binding Site Finder (CONFAC) bioinformatics software package was used to predict transcription factors associated with inflammatory genes induced following stroke and suppressed by NRG-1 treatment. NF-kappa B (NF-kB) was identified as a potential transcriptional regulator of NRG-1-suppressed genes following ischemia. The involvement of specific NF-kB subunits in NRG-1-mediated inflammatory responses was examined using N9 microglial cells pre-treated with NRG-1 (100 ng/ml) followed by lipopolysaccharide (LPS; 10 μg/ml) stimulation. The effects of NRG-1 on cytokine production were investigated using Luminex technology. The levels of the p65, p52, and RelB subunits of NF-kB and IkB-α were determined by western blot analysis and ELISA. Phosphorylation of IkB-α was investigated by ELISA. Results CONFAC identified 12 statistically over-represented transcription factor-binding sites (TFBS) in our dataset, including NF-kBP65. Using N9 microglial cells, we observed that NRG-1 significantly inhibited LPS-induced TNFα and IL-6 release. LPS increased the phosphorylation and degradation of IkB-α which was blocked by NRG-1. NRG-1 also prevented the nuclear translocation of the NF-kB p65 subunit following LPS administration. However, NRG-1 increased production of the neuroprotective cytokine granulocyte colony-stimulating factor (G-CSF) and the nuclear translocation of the NF-kB p52 subunit, which is associated with the induction of anti-apoptotic and suppression of pro-inflammatory gene expression. Conclusions Neuroprotective and anti-inflammatory effects of NRG-1 are associated with the differential regulation of NF-kB signaling pathways in microglia. Taken together, these findings suggest that NRG-1 may be a potential therapeutic treatment for treating stroke and other neuroinflammatory disorders.

Alfalfa represents one of the most important legume forages, and it is also applied as an organic fertilizer to improve soil quality. However, this perennial plant is native to warmer temperate regions, and its valuable cold-acclimation-related regulatory mechanisms are still less known. In higher plants, the bHLH transcription factors play pleiotropic regulatory roles in response to abiotic stresses. The recently released whole genome sequencing data of alfalfa allowed us to identify 469 MsbHLHs by multi-step homolog search. Herein, we primarily identified 65 MsbHLH genes that significantly upregulated under cold stress, and such bHLHs were classified into six clades according to their expression patterns. Interestingly, the phylogenetic analysis and conserved motif screening of the cold-induced MsbHLHs showed that the expression pattern is relatively varied in each bHLH subfamily, this result indicating that the 65 MsbHLHs may be involved in a complex cold-responsive regulatory network. Hence, we analyzed the TFBSs at promoter regions that unraveled a relatively conserved TFBS distribution with genes exhibiting similar expression patterns. Eventually, to verify the core components involved in long-term cold acclimation, we examined transcriptome data from a freezing-tolerant species (cv. Zhaodong) in the field and compared the expression of cold-sensitive/tolerant subspecies of alfalfa, giving 11 bHLH as candidates, which could be important for further cold-tolerance enhancement and molecular breeding through genetic engineering in alfalfa.

Abstract Changes in transcription factor binding sites (TFBSs) can alter the spatiotemporal expression pattern and transcript abundance of genes. Loss and gain of TFBSs were shown to cause shifts in expression patterns in numerous cases. However, we know little about the evolution of extended regulatory sequences incorporating many TFBSs. We compare, across the crucifers (Brassicaceae, cabbage family), the sequences between the translated regions of Arabidopsis Bsister (ABS)-like MADS-box genes (including paralogous GOA-like genes) and the next gene upstream, as an example of family-wide evolution of putative upstream regulatory regions (PURRs). ABS-like genes are essential for integument development of ovules and endothelium formation in seeds of Arabidopsis thaliana. A combination of motif-based gene ontology enrichment and reporter gene analysis using A. thaliana as common trans-regulatory environment allows analysis of selected Brassicaceae Bsister gene PURRs. Comparison of TFBS of transcriptionally active ABS-like genes with those of transcriptionally largely inactive GOA-like genes shows that the number of in silico predicted TFBS) is similar between paralogs, emphasizing the importance of experimental verification for in silico characterization of TFBS activity and analysis of their evolution. Further, our data show highly conserved expression of Brassicaceae ABS-like genes almost exclusively in the chalazal region of ovules. The Arabidopsis-specific insertion of a transposable element (TE) into the ABS PURRs is required for stabilizing this spatially restricted expression, while other Brassicaceae achieve chalaza-specific expression without TE insertion. We hypothesize that the chalaza-specific expression of ABS is regulated by cis-regulatory elements provided by the TE.

Safflower (Carthamus tinctorius L.) is known for its oil quality and ability to grow in drought conditions. The threat to global food security posed by challenges of climate change has stressed the use of functional genomics in current plant breeding approaches. Plant steroid hormones called brassinosteroids (BRs) are at the nexus of regulating plant growth and development, and plant stress responses. Enhanced BR levels or signalling have increased crop yields by up to 40% while also conferring broad range stress tolerance. Currently there is no information on the BR biosynthesis and signalling pathways in safflower. A de novo transcriptomic analysis of untreated and 24-epibrassinolide (EBR)-treated safflower leaves was conducted using the Illumina sequencing platform. Approximately 5 GB clean data were generated from untreated and EBR-treated samples that assembled into 34,456 and 36,997 transcripts (combined 50,630), and 30,180 and 32,333 CoDing sequences (CDS) (combined 43,637), respectively. More than 71% of the CDS were annotated with majority of hits against Cynara cardunculus var. scolymus, a thistle in the safflower family. A total of 74 KEGG pathways were identified in safflower. Six genes, including DWF4 that codes for a rate-limiting enzyme in BR biosynthesis, were mapped to the BR biosynthesis pathway using the KEGG mapper.

Unveiling the complexities of gene expression regulation, the study explores the intricate DNA‐binding mechanisms of transcription factors (TFs). By employing the KaScape method previously developed to measure both bound and unbound populations at thermodynamic equilibrium, “anchoring elements” (AEs), 3–4 base pair sequences, are identified in Arabidopsis WRKY and human PU.1 TFs crucial for binding affinity. Building on the BEESEM method, the study introduces the AEEscape algorithm, which advances the AE concept by creating a precise model of the position‐specific k‐mer binding energy landscape. This method allows for the direct identification of the dominant role of AEs from experimental data. Moreover, when integrated with genomic data, it reveals an energetic funnel around transcription factor binding sites (TFBSs), which is directly correlated with the density of AEs (AED). The findings not only offer a fresh perspective on TF‐TFBS interactions but also highlight the critical role of AED in gene regulation. These insights can pave the way for innovative strategies to manipulate gene expression. This study delineate the binding mechanism of transcription factors (TFs) in the genome with the knowledge obtained at thermodynamic equilibrium conditions. Through KaScape experiments, combined with the AEEscape algorithm development, they identified the minimal dominant interacting elements, termed as Anchoring Elements (AEs). Their findings also demonstrate that AEs and AE density are important for TF binding and genome targeting.

Despite being the third in death rate among all cancers globally, gastric carcinoma (GC) is far from being detected accurately and timely, which could benefit the prognosis. To achieve this, we performed whole-genome sequencing (WGS) to plasma cfDNA of 733 participants, including healthy individuals, patients with benign gastric diseases and GC patients. The multi-omic biomarkers in this study, including fragmentation profile, end motif and genome-wide Copy Number Variations (CNV) of plasma cfDNA, are recently developed means for cancer detection and monitoring. And these biomarkers were extracted from WGS data to build machine learning algorithm based classifiers, prediction models, to discriminate GC patients from healthy individuals, achieving extremely high precision of sensitivity at 94.87% and specificity at 99.35%. Therefore, these cfDNA multi-omic biomarkers may serve as means to detect GC accurately, affordably and timely.

AbstractThe activation of mobile genetic elements is a prerequisite for controlling the expression of genes in successive cell divisions, with their change specifically depending on the tissue and developmental stage. These activation patterns are characteristic of totipotent and pluripotent embryo cells, as well as for stem cells in the postnatal period. We have suggested that in the evolution of multicellular eukaryotes, optimal ratios are selected in the arrangement of transposons relative to exons and introns of host genes. These ratios, specific to each species, can be the basis for controlling the sequential differentiation of stem cells necessary for the development of the whole organism. Despite the fact that cell differentiation in ontogenesis is controlled by a very conservative set of genes, mobile genetic elements are involved in the fine-tuning of regulatory networks that control the expression of these genes, which is reflected in the phenotypic characteristics of each species. Transposons are important sources of genome structures that are actively used to regulate the multicellular embryonic development. These structures include binding sites with transcription factors, enhancers and silencers, promoters, insulators, alternative splicing sites, non-coding RNA. Moreover, transposons are involved in the emergence and evolution of new protein-coding genes through exonization, domestication, and the formation of retrogenes. The activation of transposons is needed to regulate the differentiation and reproduction of cells in the body; however, in terminally differentiated cells, upon reaching predetermined sizes of organs, molecular systems are activated that block a further cascade of transposon activation. We suggest that the imperfection of systems aimed at specific suppression of transposon activity in mature cells may be the cause of aging and age-related diseases due to the pathological activation of mobile genetic elements. Identifying the tissue-specific mechanisms of inherited transposon activation in stem cells, as well as their pathological activation in terminally differentiated cells, may be the basis for finding ways to fight aging.

The formation of diverse cell types from an invariant set of genes is governed by biochemical and molecular processes that regulate gene activity. A complete understanding of the regulatory mechanisms of gene expression is the major function of genomics. Computational genomics is a rapidly emerging area for deciphering the regulation of metazoan genes as well as interpreting the results of high-throughput screening. The integration of computer science with biology has expedited molecular modelling and processing of large-scale data inputs such as microarrays, analysis of genomes, transcriptomes and proteomes. Many bioinformaticians have developed various algorithms for predicting transcriptional regulatory mechanisms from the sequence, gene expression and interaction data. This review contains compiled information of various computational methods adopted to dissect gene expression pathways.