Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

{"title":"Transcriptional responses of three slc39a/zip members (zip4, zip5 and zip9) and their roles in Zn metabolism in grass carp (Ctenopharyngodon idella).","authors":"Jia-Cheng Guo, Peng-Cheng Xu, Yi-Chuang Xu, Tian-Hua Zhang, Lu-Lu Liu, Tao Liu, Zhi Luo","doi":"10.1016/j.bbagrm.2024.195075","DOIUrl":"10.1016/j.bbagrm.2024.195075","url":null,"abstract":"<p><p>In order to explore the regulatory mechanism of zip4, zip5 and zip9 in zinc metabolism of grass carp (Ctenopharyngodon idella), the effects of zinc (Zn) on the mRNA expression of zip4, zip5 and zip9 were investigated. Compared to the control, the mRNA levels of zip4 and zip9 were significantly reduced under low and high zinc in L8824 cells; the mRNA expression level of zip5 was significantly increased under low and high zinc incubation. Then, their promoter sequences were cloned, which were 2361 bp, 2004 bp and 2186 bp sequences for zip4, zip5 and zip9 promoters, respectively. The transcriptional activities of the three promoters had different responses to Zn treatment. The transcriptional factor signal transducer and activator of transcription 3 (STAT3) had specific binding sites at -1111/-1121 bp of zip5 promoter and at -1679/-1689 bp of zip9 promoter. Similarly, krüppel-like factor 4 (KLF4) could specifically bind to the -599/-609 bp sequence on the zip5 promoter and the -261/-272 bp sequence on the zip9 promoter. The results of electrophoretic mobility-shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) indicated that Zn incubation increased DNA binding capacity of STAT3 to zip5 and zip9 promoters, and decreased DNA binding capacity of KLF4 to zip5 and zip9 promoters. This study provides a good basis for elucidating the regulatory mechanism of zinc metabolism in the vertebrates.</p>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":" ","pages":"195075"},"PeriodicalIF":2.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental approaches to investigate biophysical interactions between homeodomain transcription factors and DNA.","authors":"Fadwa Mekkaoui, Robert A Drewell, Jacqueline M Dresch, Donald E Spratt","doi":"10.1016/j.bbagrm.2024.195074","DOIUrl":"10.1016/j.bbagrm.2024.195074","url":null,"abstract":"<p><p>Homeodomain transcription factors (TFs) bind to specific DNA sequences to regulate the expression of target genes. Structural work has provided insight into molecular identities and aided in unraveling structural features of these TFs. However, the detailed affinity and specificity by which these TFs bind to DNA sequences is still largely unknown. Qualitative methods, such as DNA footprinting, Electrophoretic Mobility Shift Assays (EMSAs), Systematic Evolution of Ligands by Exponential Enrichment (SELEX), Bacterial One Hybrid (B1H) systems, Surface Plasmon Resonance (SPR), and Protein Binding Microarrays (PBMs) have been widely used to investigate the biochemical characteristics of TF-DNA binding events. In addition to these qualitative methods, bioinformatic approaches have also assisted in TF binding site discovery. Here we discuss the advantages and limitations of these different approaches, as well as the benefits of utilizing more quantitative approaches, such as Mechanically Induced Trapping of Molecular Interactions (MITOMI), Microscale Thermophoresis (MST) and Isothermal Titration Calorimetry (ITC), in determining the biophysical basis of binding specificity of TF-DNA complexes and improving upon existing computational approaches aimed at affinity predictions.</p>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":" ","pages":"195074"},"PeriodicalIF":2.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Competing endogenous RNAs network and therapeutic implications: New horizons in disease research.","authors":"Nahla E El-Ashmawy, Eman G Khedr, Renad T Darwish, Amera O Ibrahim","doi":"10.1016/j.bbagrm.2024.195073","DOIUrl":"10.1016/j.bbagrm.2024.195073","url":null,"abstract":"<p><p>Different diseases may arise from the dysregulation of non-coding RNAs (ncRNAs), which regulation is necessary for maintaining cellular homeostasis. ncRNAs are regulated by transcriptional, post-transcriptional, translational and post-translational processes. Post-transcriptional regulation of gene expression is carried out by microRNAs (miRNAs), a class of small ncRNA molecules, which can identify their target sites by a brief nucleotide sequence, known as the miRNA response element (MRE), present on the miRNA seed sequence and the target transcript. This binding between miRNAs and targets can regulate the gene expression through inhibition of translation or degradation of target messenger RNA (mRNA). The transcripts that share MREs can be involved in competition for the central miRNA pool, which could have an indirect impact on each other's regulation. This competition network is called competing endogenous RNAs network (ceRNET). Many ncRNAs, including circular RNA, pseudogene, and long non-coding RNA, as well as mRNA, a coding RNA transcript, make up ceRNET. These components play a crucial role in post-transcriptional regulation and are involved in the diagnosis and treatment of many pathological disorders. The mechanism of ceRNET and its essential components, as well as their therapeutic implications in different diseases such as cancer, diabetes mellitus, neurological, cardiovascular, hepatic and respiratory disorders were covered in this review.</p>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":" ","pages":"195073"},"PeriodicalIF":2.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatic meta-analysis of transcriptomics of developing Drosophila muscles identifies temporal regulatory transcription factors including a Notch effector","authors":"Amartya Mukherjee ,&nbsp;Fathima Ashraf ,&nbsp;Upendra Nongthomba","doi":"10.1016/j.bbagrm.2024.195066","DOIUrl":"10.1016/j.bbagrm.2024.195066","url":null,"abstract":"<div><div>The intricate mechanism of gene regulation coordinates the precise control of when, where, and to what extent genes are activated or repressed, directing the complex processes that govern cellular functions and development. Dysregulation of gene expression can lead to diseases such as autoimmune disorders, cancer, and neurodegeneration. Transcriptional regulation, especially involving transcription factors (TFs), plays a major role in controlling gene expression. This study focuses on identifying gene regulatory mechanisms that generate distinct gene expression patterns during <em>Drosophila</em> muscle development. Utilising a bioinformatics approach, we analysed the developmental time-point-specific transcriptomics resource generated by Spletter <em>et al</em>., which includes mRNA sequencing data at eight stages of indirect flight muscle (IFM) development. They had identified 40 distinct genome-wide clusters representing various temporal expression dynamics using 'soft' clustering. Promoter sequences of genes in these clusters were analysed to predict novel motifs that act as TF binding sites. Comparative analysis with known motifs revealed significant overlaps, indicating shared transcriptional regulation. The physiological relevance of predicted TFs was confirmed by cross-referencing with experimental ChIP-seq data. We focused on Cluster 36, characterised by a unique bimodal temporal expression profile, and identified candidate genes, <em>Rbfox1</em> and <em>zfh1</em>, for further study. Ectopic overexpression experiments revealed that the TF Enhancer of split m8 helix-loop-helix [E(spl)m8-HLH], part of the Notch signalling pathway, acts as a transcriptional repressor for <em>Rbfox1</em> and <em>zfh1</em>. Our findings highlight the complexity of transcriptional regulation during myogenesis, and identify key TFs that could be targeted for further research in muscle development and related disorders.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 1","pages":"Article 195066"},"PeriodicalIF":2.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCL11b interacts with RNA and proteins involved in RNA processing and developmental diseases","authors":"Haitham Sobhy ,&nbsp;Marco De Rovere ,&nbsp;Amina Ait-Ammar ,&nbsp;Muhammad Kashif ,&nbsp;Clementine Wallet ,&nbsp;Fadoua Daouad ,&nbsp;Thomas Loustau ,&nbsp;Carine Van Lint ,&nbsp;Christian Schwartz ,&nbsp;Olivier Rohr","doi":"10.1016/j.bbagrm.2024.195065","DOIUrl":"10.1016/j.bbagrm.2024.195065","url":null,"abstract":"<div><div>BCL11b is a transcription regulator and a tumor suppressor involved in lymphomagenesis, central nervous system (CNS) and immune system developments. BCL11b favors persistence of HIV latency and contributes to control cell cycle, differentiation and apoptosis in multiple organisms and cell models. Although BCL11b recruits the non-coding RNA 7SK and epigenetic enzymes to regulate gene expression, BCL11b-associated ribonucleoprotein complexes are unknown. Thanks to CLIP-seq and quantitative LC-MS/MS mass spectrometry approaches complemented with systems biology validations, we show that BCL11b interacts with RNA splicing and non-sense-mediated decay proteins, including FUS, SMN1, UPF1 and Drosha, which may contribute in isoform selection of protein-coding RNA isoforms from noncoding-RNAs isoforms (retained introns or nonsense mediated RNA). Interestingly, BCL11b binds to RNA transcripts and proteins encoded by the same genes (FUS, ESWR1, CHD and Tubulin). Our study highlights that BCL11b targets RNA processing and splicing proteins, and RNAs that implicate cell cycle, development, neurodegenerative, and cancer pathways. These findings will help future mechanistic understanding of developmental disorders.</div></div><div><h3>Importance</h3><div>BCL11b-protein and RNA interactomes reveal BLC11b association with specific nucleoprotein complexes involved in the regulation of genes expression.</div><div>BCL11b interacts with RNA processing and splicing proteins.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195065"},"PeriodicalIF":2.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human stem cell-specific epigenetic signatures control transgene expression","authors":"Chulhwan S. Kwak,&nbsp;Furkan E. Oflaz,&nbsp;Jiamin Qiu,&nbsp;Xinnan Wang","doi":"10.1016/j.bbagrm.2024.195063","DOIUrl":"10.1016/j.bbagrm.2024.195063","url":null,"abstract":"<div><div>Human stem cell-derived models have emerged as an important platform to study tissue differentiation and disease mechanisms. Those models could capitalize on biochemical and cell biological methodologies such as omics, autophagy, and organelle dynamics. However, epigenetic silencing in stem cells creates a barrier to apply genetically encoded tools. Here we investigate the molecular mechanisms underlying exogenously expressed gene silencing by employing multiple commonly used promoters in human induced pluripotent stem cells (iPSCs), glioblastoma cells (GBM), and embryonic kidney cells (HEK). We discover that all promoters tested are highly methylated on the CpG island regions with lower protein expression in iPSCs, as compared to non-iPSCs. Elongation factor 1 alpha short (EF1α short or EFS) promoter, which has fewer CpG island number compared to the other promoters, can drive relatively higher gene expression in iPSCs, despite CpG methylation. Adding a minimal A2 ubiquitous chromatin opening element (minimal A2 UCOE or miniUCOE) upstream of a promoter inhibits CpG methylation and enhances gene expression in iPSCs. Our results demonstrate stem cell type-specific epigenetic modification of transgenic promoter region and provide useful information for designing anti-silencing strategies to increase transgene expression in iPSCs.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195063"},"PeriodicalIF":2.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EBV infection alters DNA methylation in primary human colon cells: A path to inflammation and carcinogenesis?","authors":"Roberta Santarelli ,&nbsp;Giuseppe Rubens Pascucci ,&nbsp;Salvatore Lo Presti ,&nbsp;Michele Di Crosta ,&nbsp;Rossella Benedetti ,&nbsp;Alessia Neri ,&nbsp;Roberta Gonnella ,&nbsp;Mara Cirone","doi":"10.1016/j.bbagrm.2024.195064","DOIUrl":"10.1016/j.bbagrm.2024.195064","url":null,"abstract":"<div><div>Epstein-Barr Virus (EBV) is associated with several types of human cancers, and changes in DNA methylation are reported to contribute to viral-driven carcinogenesis, particularly in cancers of epithelial origin. In a previous study, we demonstrated that EBV infects human primary colonic cells (HCoEpC) and replicates within these cells, leading to pro-inflammatory and pro-tumorigenic effects. Notably, these effects were mostly prevented by inhibiting viral replication with PAA. Interestingly, the EBV-induced effects correlated with the upregulation of DNMT1 and were counteracted by pretreating cells with 5-AZA, suggesting a role for DNA hypermethylation.</div><div>Building on this background, the current study investigates the methylation changes induced by EBV infection in HCoEpC, both in the presence and absence of PAA, or ERK1/2 and STAT3 inhibitors, pathways known to be activated by EBV and involved in the dysregulation of methylation in tumor cells. The genome-wide methylation analysis conducted in this study allowed us to identify several biological processes and genes affected by these epigenetic changes, providing insights into the possible underlying mechanisms leading to the pathological effects induced by EBV. Specifically, we found that the virus induced significant methylation changes, with hypermethylation being more prevalent than hypomethylation. Several genes involved in embryogenesis, carcinogenesis, and inflammation were affected.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195064"},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning based analysis of single-cell data reveals evidence of subject-specific single-cell gene expression profiles in acute myeloid leukaemia patients and healthy controls","authors":"Andreas Chrysostomou ,&nbsp;Cristina Furlan,&nbsp;Edoardo Saccenti","doi":"10.1016/j.bbagrm.2024.195062","DOIUrl":"10.1016/j.bbagrm.2024.195062","url":null,"abstract":"<div><div>Acute Myeloid Leukaemia (AML) is characterized by uncontrolled growth of immature myeloid cells, disrupting normal blood production. Treatment typically involves chemotherapy, targeted therapy, and stem cell transplantation but many patients develop chemoresistance, leading to poor outcomes due to the disease's high heterogeneity. In this study, we used publicly available single-cell RNA sequencing data and machine learning to classify AML patients and healthy, monocytes, dendritic and progenitor cells population. We found that gene expression profiles of AML patients and healthy controls can be classified at the individual level with high accuracy (&gt;70 %) when using progenitor cells, suggesting the existence of subject-specific single cell transcriptomics profiles. The analysis also revealed molecular determinants of patient heterogeneity (e.g. TPSD1, CT45A1, and GABRA4) which could support new strategies for patient stratification and personalized treatment in leukaemia.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195062"},"PeriodicalIF":2.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNAs in ubiquitination, protein degradation, and human diseases","authors":"Prarthana Guha,&nbsp;Avisankar Chini,&nbsp;Ashcharya Rishi,&nbsp;Subhrangsu S. Mandal","doi":"10.1016/j.bbagrm.2024.195061","DOIUrl":"10.1016/j.bbagrm.2024.195061","url":null,"abstract":"<div><div>Protein stability and turnover is critical in normal cellular and physiological process and their misregulation may contribute to accumulation of unwanted proteins causing cellular malfunction, neurodegeneration, mitochondrial malfunction, and disrupted metabolism. Signaling mechanism associated with protein degradation is complex and is extensively studied. Many protein and enzyme machineries have been implicated in regulation of protein degradation. Despite these insights, our understanding of protein degradation mechanisms remains limited. Emerging studies suggest that long non-coding RNAs (lncRNAs) play critical roles in various cellular and physiological processes including metabolism, cellular homeostasis, and protein turnover. LncRNAs, being large nucleic acids (&gt;200 nt long) can interact with various proteins and other nucleic acids and modulate protein structure and function leading to regulation of cell signaling processes. LncRNAs are widely distributed across cell types and may exhibit tissue specific expression. They are detected in body fluids including blood and urine. Their expressions are also altered in various human diseases including cancer, neurological disorders, immune disorder, and others. LncRNAs are being recognized as novel biomarkers and therapeutic targets. This review article focuses on the emerging role of noncoding RNAs (ncRNAs), particularly long noncoding RNAs (lncRNAs), in the regulation of protein polyubiquitination and proteasomal degradation.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195061"},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of gene expression at the post-translational modification level","authors":"Guoqiang Xu ,&nbsp;Yu-Sheng Cong ,&nbsp;Sudipto Das","doi":"10.1016/j.bbagrm.2024.195060","DOIUrl":"10.1016/j.bbagrm.2024.195060","url":null,"abstract":"","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195060"},"PeriodicalIF":2.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}