Oscar Rodríguez-Lima, Juan Rodrigo Salazar, Laura A Velázquez-Villegas, María Fernanda Pérez-Téllez, Alonso Méndez-Pérez, Lucía Jiménez, Ricardo Miranda-Blancas, Elisa Heredia-Gómez, Marco A Loza-Mejía, Abraham Landa
{"title":"Analysis of the interaction of TATA-box binding protein 1 and 2 from <i>Taenia solium</i> to TATA-box: structural factors related to selectivity and affinity.","authors":"Oscar Rodríguez-Lima, Juan Rodrigo Salazar, Laura A Velázquez-Villegas, María Fernanda Pérez-Téllez, Alonso Méndez-Pérez, Lucía Jiménez, Ricardo Miranda-Blancas, Elisa Heredia-Gómez, Marco A Loza-Mejía, Abraham Landa","doi":"10.1080/21541264.2025.2567199","DOIUrl":"https://doi.org/10.1080/21541264.2025.2567199","url":null,"abstract":"<p><p>TATA-box binding protein (TBP) is a core subunit of the transcription factor TFIID and plays a pivotal role in recognizing the TATA-box in protein-coding genes, facilitating the assembly of the transcription preinitiation complex. In <i>Taenia solium</i>, only one TBP isoform (TsTBP1) has been previously reported. Here, we identify and characterize a second isoform, TsTBP2, using a combination of molecular biology and bioinformatics approaches. TsTBP2 shares 42% primary sequence identity with TsTBP1 and exhibits distinct expression patterns between cysticerci and adult stages. To investigate the molecular determinants of DNA recognition, selectivity, and binding affinity, we performed molecular docking and molecular dynamics simulations for both TsTBPs with various TATA-box sequences. Our results reveal that TsTBP1 exhibits higher affinity for <i>T. solium</i> TATA-box sequences compared to the consensus AdML TATA-box (TATAAAAG), largely due to the specific interaction of critical phenylalanine residues with the DNA minor groove, which induces DNA bending and stabilizes the TBP-DNA complex. Furthermore, analysis of the Buckle parameter indicates that these Phe residues are the principal contributors to DNA distortion. To our knowledge, this study represents the first analysis of TBP selectivity and affinity in cestodes, providing insights into the molecular mechanisms underlying transcriptional regulation in <i>T. solium</i>.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-16"},"PeriodicalIF":4.4,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcriptional regulation of gene modules in Epstein-Barr virus.","authors":"Paul M Lieberman","doi":"10.1080/21541264.2025.2562704","DOIUrl":"https://doi.org/10.1080/21541264.2025.2562704","url":null,"abstract":"<p><p>Epstein-Barr Virus (EBV) establishes life-long latent infection in >90% of adults and is a causal agent for diverse cancers and autoimmune diseases. EBV has a complex life cycle in multiple different tissue types that involve dynamic variations in viral gene expression. These gene expression changes account for the success of the virus in long-term persistence and evading host immune control, as well as its potential for driving cancer evolution and autoimmune disease. Here, we review some of the salient features of EBV gene regulation highlighting the many variations of viral transcription. We review recent advances in our understanding of the factors that bind and regulate EBV gene expression. Based on this diversity of viral transcription patterns, we propose that EBV genome consists of gene modules regulated by local promoter-proximal transcription factor combinations that are further regulated by distal regulatory interactions among the various modules that interact through architectural factors, such as CTCF and cohesion. These modules are likely to represent chromatin architectural domains, and can also interact with host chromosome domains that further regulate viral and host gene expression. We propose that this gene regulatory hierarchy provides EBV with necessary plasticity for viral persistence, as well as a strong potentiator for cancer and autoimmune disease.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-21"},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CGGBP1 from higher amniotes restricts cytosine methylation and drives a GC-bias in transcription factor-binding sites at repressed promoters.","authors":"Praveen Kumar, Ishani Morbia, Aditi Lakshmi Satish, Subhamoy Datta, Umashankar Singh","doi":"10.1080/21541264.2025.2533598","DOIUrl":"https://doi.org/10.1080/21541264.2025.2533598","url":null,"abstract":"<p><p>CGGBP1, a 20 kDa protein, has several functions associated with its DNA-binding through a C2H2 zinc finger. A range of studies have shown that GC richness, inter-strand G/C-skew and low cytosine methylation are associated with CGGBP1 occupancy. The non-preference of any sequence motif as CGGBP1 binding site suggests widespread association of CGGBP1 with DNA including at potent transcription factor-binding sites (TFBSs) in promoter regions. The evolutionary advantage of such a design remains unclear. The regulatory interference by human CGGBP1 at TFBSs is supported by purifying selection in the DNA-binding domain of CGGBP1 and its requirement for gene repression as well as restriction of cytosine methylation at GC-rich TFBSs. Here, we describe an evolutionary trajectory of this property of CGGBP1 by combining global gene expression and cytosine methylation analyses on human cells expressing CGGBPs from four different vertebrates (representatives of coelacanth, reptiles, aves and mammals). We discover a potent cytosine methylation restriction by human CGGBP1 at some GC-rich TFBSs in repressed promoters. Further, we combine a high-throughput analysis of GC compositional bias of these CGGBP-regulated TFBSs from available orthologous sequences from a pool of over 100 species. We show that cytosine methylation restriction by CGGBP1 is tightly linked to GC retention in a set of TFBSs. Our experiments using four representative and three consensus forms of CGGBPs and orthology analyses of target gene promoters indicate that this property of CGGBPs has most likely evolved in higher amniotes (aves and mammals) with lineage-specific heterogeneities in lower amniotes (reptiles). ChIP-seq and C-T transition analysis in MeDIP-seq suggest that occupancy of CGGBP1 at these target TFBSs plays a crucial role in their low methylation, GC-biased evolution and associated functions in gene repression.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-36"},"PeriodicalIF":4.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transcription-AustinPub Date : 2025-04-01Epub Date: 2025-07-11DOI: 10.1080/21541264.2025.2521764
Harlan R Barker, Seppo Parkkila, MarttiE E Tolvanen
{"title":"TFBSFootprinter: a multiomics tool for prediction of transcription factor binding sites in vertebrate species.","authors":"Harlan R Barker, Seppo Parkkila, MarttiE E Tolvanen","doi":"10.1080/21541264.2025.2521764","DOIUrl":"10.1080/21541264.2025.2521764","url":null,"abstract":"<p><strong>Background: </strong>Transcription factor (TF) proteins play a critical role in the regulation of eukaryotic gene expression via sequence-specific binding to genomic locations known as transcription factor binding sites (TFBSs). Accurate prediction of TFBSs is essential for understanding gene regulation, disease mechanisms, and drug discovery. These studies are therefore relevant not only in humans but also in model organisms and domesticated and wild animals. However, current tools for the automatic analysis of TFBSs in gene promoter regions are limited in their usability across multiple species. To our knowledge, no tools currently exist that allow for automatic analysis of TFBSs in gene promoter regions for many species.</p><p><strong>Methodology and findings: </strong>The TFBSFootprinter tool combines multiomic transcription-relevant data for more accurate prediction of functional TFBSs in 317 vertebrate species. In humans, this includes vertebrate sequence conservation (GERP), proximity to transcription start sites (FANTOM5), correlation of expression between target genes and TFs predicted to bind promoters (FANTOM5), overlap with ChIP-Seq TF metaclusters (GTRD), overlap with ATAC-Seq peaks (ENCODE), eQTLs (GTEx), and the observed/expected CpG ratio (Ensembl). In non-human vertebrates, this includes GERP, proximity to transcription start sites, and CpG ratio.TFBSFootprinter analyses are based on the Ensembl transcript ID for simplicity of use and require minimal setup steps. Benchmarking of the TFBSFootprinter on a manually curated and experimentally verified dataset of TFBSs produced superior results when using all multiomic data (average area under the receiver operating characteristic curve, 0.881), compared with DeepBind (0.798), DeepSEA (0.682), FIMO (0.817) and traditional PWM (0.854). The results were further improved by selecting the best overall combination of multiomic data (0.910). Additionally, we determined combinations of multiomic data that provide the best model of binding for each TF. TFBSFootprinter is available as Conda and Python packages.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"16 2-3","pages":"204-223"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transcription-AustinPub Date : 2025-04-01Epub Date: 2025-03-04DOI: 10.1080/21541264.2025.2473224
Vijay Gahlaut, Vandana Jaiswal
{"title":"The role of lncRNA in plant growth and domestication.","authors":"Vijay Gahlaut, Vandana Jaiswal","doi":"10.1080/21541264.2025.2473224","DOIUrl":"10.1080/21541264.2025.2473224","url":null,"abstract":"<p><p>The lncRNAs have deepened our understanding of crop domestication and improvement. These regulators influence key traits like yield, germination, and stress response. Future research should identify functional lncRNAs, explore their interactions, and use CRISPR for targeted improvements. Understanding their roles in polyploid crops may enhance resilience and productivity.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"169-175"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transcription-AustinPub Date : 2025-04-01Epub Date: 2025-06-25DOI: 10.1080/21541264.2025.2521767
John Gray, Erich Grotewold
{"title":"Decoding complexity: tackling the challenge of how many transcription factors regulate a plant gene.","authors":"John Gray, Erich Grotewold","doi":"10.1080/21541264.2025.2521767","DOIUrl":"10.1080/21541264.2025.2521767","url":null,"abstract":"<p><p>The regulation of transcription is a major control point in the flow of information from the genome to the phenome. Central to this regulation are transcription factors (TFs), which bind specific DNA motifs in gene regulatory regions. In both metazoans and plants, 5-7% of all genes encode TFs. Although individual TFs can recognize and regulate thousands of target genes, an important question remains: how many TFs are required to precisely control the expression of a single gene? In this review, we compare the regulation of gene expression in plants and metazoans, outline key methodologies for identifying genes recognized or regulated by TFs, and explore what is currently known about the number of TFs needed to define the expression of any given plant gene. As the volume of high-throughput sequencing data continues to grow exponentially, it becomes increasingly clear that transcriptional regulatory networks exhibit remarkable complexity, characterized by many targets influenced by each TF; and that many TFs, often several dozens, contribute to the regulation of individual genes.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"261-283"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transcription-AustinPub Date : 2025-04-01Epub Date: 2025-03-05DOI: 10.1080/21541264.2025.2474367
Sarah B Worthan, Megan I Grant, Megan G Behringer
{"title":"Rho-dependent termination: a bacterial evolutionary capacitor for stress resistance.","authors":"Sarah B Worthan, Megan I Grant, Megan G Behringer","doi":"10.1080/21541264.2025.2474367","DOIUrl":"10.1080/21541264.2025.2474367","url":null,"abstract":"<p><p>Since the Modern Synthesis, interest has grown in resolving the \"black box\" between genotype and phenotype. Contained within this black box are highly plastic RNA and proteins with global effects on chromosome integrity and gene expression that serve as evolutionary capacitors - elements that enable the accumulation and buffering of genetic variation in normal conditions and reveal hidden genetic variation when induced by environmental stress. Discussion of evolutionary capacitors has primarily focused on eukaryotic translation factors and chaperones, such as Hsp90 and PSI+ prion. However, due to the coupling of transcription and translation in prokaryotes, transcription factors can be equally impactful in the modulation of gene expression and phenotypes. In this review, we discuss the prokaryotic transcription terminator Rho and how mutagenesis and plasticity of Rho influence epistasis, evolvability, and adaptation to stress in bacteria. We discuss the effects of variation in Rho generated by nature, laboratory mutagenesis, and experimental evolution; and how this variation is constrained or encouraged by Rho's extensive network of protein interactors. Exploring Rho's role as an evolutionary capacitor, along with identifying additional elements that can serve this function, can significantly advance our understanding of how organisms adapt to thrive in diverse environments.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"176-189"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transcription-AustinPub Date : 2025-04-01Epub Date: 2025-07-11DOI: 10.1080/21541264.2025.2521766
Stephen Safe, Arafat R Oany, Wai Ning Tsui, Miok Lee, Vinod Srivastava, Srijana Upadhyay, Amanuel Hailemariam, Evan Farkas, Sarah Kakwan, Caitrina Kearns, Gargi Sivaram
{"title":"Orphan nuclear receptor transcription factors as drug targets.","authors":"Stephen Safe, Arafat R Oany, Wai Ning Tsui, Miok Lee, Vinod Srivastava, Srijana Upadhyay, Amanuel Hailemariam, Evan Farkas, Sarah Kakwan, Caitrina Kearns, Gargi Sivaram","doi":"10.1080/21541264.2025.2521766","DOIUrl":"10.1080/21541264.2025.2521766","url":null,"abstract":"<p><p>The nuclear receptor (NR) superfamily of ligand-activated receptors plays a key role in maintaining cellular homeostasis and in pathophysiology. NRs can be subdivided into functional activities structural similarity and the existence of endogenous ligands. Most NRs are classified as those that are adopted orphan or orphan receptors which have only possible ligands or no identified endogenous ligands, respectively. In this review, the activities of the complete orphan receptor sub-family of transcription factors have been reviewed with a focus on the effects of possible endogenous (biochemicals), natural product-derived and synthetic ligands. Despite their lack of a bona-fide ligand, the orphan receptors bind structurally diverse compounds that exhibit tissue-specific agonist, antagonist and inverse agonist activities with potential for future development as clinical therapeutics for the treatment of multiple diseases.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"16 2-3","pages":"224-260"},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transcription-AustinPub Date : 2025-04-01Epub Date: 2025-03-12DOI: 10.1080/21541264.2025.2476848
Robin Brice, Zhengxin Wang
{"title":"GATA3 and E2F6 negatively regulate WDR77 expression to inhibit prostate cancer cell growth.","authors":"Robin Brice, Zhengxin Wang","doi":"10.1080/21541264.2025.2476848","DOIUrl":"10.1080/21541264.2025.2476848","url":null,"abstract":"<p><p>The WD repeat domain 77 (WDR77) protein plays a critical role in prostate development and dysregulation of WDR77 expression is associated with prostate tumorigenesis. This study investigated the regulatory effects of GATA3 and E2F6 on WDR77 gene expression. A negative correlation between GATA3/E2F6 and WDR77 expression at both mRNA and protein levels was observed during prostate development and prostate tumorigenesis. Prostate cancer cells lost expression of GATA3 and E2F6 and re-expression of GATA3 and E2F6 resulted in a dose-dependent reduction in WDR77 expression and cell growth. Exogenous expression of WDR77 relieved the growth inhibition by GATA3. GATA3 and E2F6 directly interact with the promoter of the WDR77 gene in vitro and in vivo and repress WDR77 promoter activity. These results provide valuable insights into the molecular mechanisms governing WDR77 expression during prostate development and prostate tumorigenesis.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"190-203"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transcription-AustinPub Date : 2025-02-01Epub Date: 2025-02-14DOI: 10.1080/21541264.2025.2460249
Joaquin M Espinosa
{"title":"Harnessing transcription factors for therapeutic purposes.","authors":"Joaquin M Espinosa","doi":"10.1080/21541264.2025.2460249","DOIUrl":"10.1080/21541264.2025.2460249","url":null,"abstract":"","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-2"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}