Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

{"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}

{"title":"Uncovering the functions and mechanisms of regulatory elements-associated non-coding RNAs","authors":"Olivier Fosseprez,&nbsp;Olivier Cuvier","doi":"10.1016/j.bbagrm.2024.195059","DOIUrl":"10.1016/j.bbagrm.2024.195059","url":null,"abstract":"<div><p>Over the past decade, regulatory non-coding RNAs (ncRNAs) produced by RNA Pol II have been revealed as meaningful players in various essential cellular functions. In particular, thousands of ncRNAs are produced at transcriptional regulatory elements such as enhancers and promoters, where they may exert multiple functions to regulate proper development, cellular programming, transcription or genomic stability. Here, we review the mechanisms involving these regulatory element-associated ncRNAs, and particularly enhancer RNAs (eRNAs) and PROMoter uPstream Transcripts (PROMPTs). We contextualize the mechanisms described to the processing and degradation of these short lived RNAs. We summarize recent findings explaining how ncRNAs operate locally at promoters and enhancers, or further away, either shortly after their production by RNA Pol II, or through post-transcriptional stabilization. Such discoveries lead to a converging model accounting for how ncRNAs influence cellular fate, by acting on transcription and chromatin structure, which may further involve factors participating to 3D nuclear organization.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195059"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874939924000555/pdfft?md5=a719d7cce4914187f6a9ae2d68dbcc63&pid=1-s2.0-S1874939924000555-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127452","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":"Normalization of gene counts affects principal components-based exploratory analysis of RNA-sequencing data","authors":"Henk J. van Lingen,&nbsp;Maria Suarez-Diez,&nbsp;Edoardo Saccenti","doi":"10.1016/j.bbagrm.2024.195058","DOIUrl":"10.1016/j.bbagrm.2024.195058","url":null,"abstract":"<div><p>Normalization of gene expression count data is an essential step of in the analysis of RNA-sequencing data. Its statistical analysis has been mostly addressed in the context of differential expression analysis, that is in the univariate setting. However, relationships among genes and samples are better explored and quantified using multivariate exploratory data analysis tools like Principal Component Analysis (PCA). In this study we investigate how normalization impacts the PCA model and its interpretation, considering twelve different widely used normalization methods that were applied on simulated and experimental data. Correlation patterns in the normalized data were explored using both summary statistics and Covariance Simultaneous Component Analysis. The impact of normalization on the PCA solution was assessed by exploring the model complexity, the quality of sample clustering in the low-dimensional PCA space and gene ranking in the model fit to normalized data. PCA models upon normalization were interpreted in the context gene enrichment pathway analysis. We found that although PCA score plots are often similar independently form the normalization used, biological interpretation of the models can depend heavily on the normalization method applied.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195058"},"PeriodicalIF":2.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874939924000543/pdfft?md5=6c80095a6aa1d7d87e5ef95c4f8180b2&pid=1-s2.0-S1874939924000543-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001419","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":"Crosstalk between circular RNAs and the STAT3 signaling pathway in human cancer","authors":"Mansour Almouh ,&nbsp;Chadi Soukkarieh ,&nbsp;Morshed Kassouha ,&nbsp;Samer Ibrahim","doi":"10.1016/j.bbagrm.2024.195051","DOIUrl":"10.1016/j.bbagrm.2024.195051","url":null,"abstract":"<div><p>Circular RNAs (circRNAs) are endogenous covalently closed single-stranded RNAs produced by reverse splicing of pre-mRNA. Emerging evidence suggests that circRNAs contribute to cancer progression by modulating the oncogenic STAT3 signaling pathway, which plays key roles in human malignancies. STAT3 signaling-related circRNAs expression appears to be extensively dysregulated in diverse cancer types, where they function either as tumor suppressors or oncogenes. However, the biological effects of STAT3 signaling-related circRNAs and their associations with cancer have not been systematically studied before. Given this, shedding light on the interaction between circRNAs and STAT3 signaling pathway in human malignancies may provide several novel insights into cancer therapy. In this review, we provide a comprehensive introduction to the molecular mechanisms by which circRNAs regulate STAT3 signaling in cancer progression, and the crosstalk between STAT3 signaling-related circRNAs and other signaling pathways. We also further discuss the role of the circRNA/STAT3 axis in cancer chemotherapy sensitivity.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195051"},"PeriodicalIF":2.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914584","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}