Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

{"title":"Transcriptional regulation of Znt family members znt4, znt5 and znt10 and their function in zinc transport in yellow catfish (Pelteobagrus fulvidraco)","authors":"Lu-Lu Liu ,&nbsp;Chang-Chun Song ,&nbsp;Nermeen Abu-Elala ,&nbsp;Xiao-Ying Tan ,&nbsp;Tao Zhao ,&nbsp;Hua Zheng ,&nbsp;Hong Yang ,&nbsp;Zhi Luo","doi":"10.1016/j.bbagrm.2024.195041","DOIUrl":"10.1016/j.bbagrm.2024.195041","url":null,"abstract":"<div><p>The study characterized the transcriptionally regulatory mechanism and functions of three zinc (Zn) transporters (<em>znt4</em>, <em>znt5</em> and <em>znt10</em>) in Zn²⁺ metabolism in yellow catfish (<em>Pelteobagrus fulvidraco</em>), commonly freshwater fish in China and other countries. We cloned the sequences of <em>znt4</em> promoter, spanning from −1217 bp to +80 bp relative to TSS (1297 bp); <em>znt5</em>, spanning from −1783 bp to +49 bp relative to TSS (1832 bp) and <em>znt10</em>, spanning from −1923 bp to +190 bp relative to TSS (2113 bp). In addition, after conducting the experiments of sequential deletion of promoter region and mutation of potential binding site, we found that the Nrf2 binding site (−607/−621 bp) and Klf4 binding site (−5/−14 bp) were required on <em>znt4</em> promoter, the Mtf-1 binding site (−1674/−1687 bp) and Atf4 binding site (−444/−456 bp) were required on <em>znt5</em> promoter and the Atf4 binding site (−905/−918 bp) was required on <em>znt10</em> promoter. Then, according to EMSA and ChIP, we found that Zn²⁺ incubation increased DNA affinity of Atf4 to <em>znt5</em> or <em>znt10</em> promoter, but decreased DNA affinity of Nrf2 to <em>znt4</em> promoter, Klf4 to <em>znt4</em> promoter and Mtf-1 to <em>znt5</em> promoter. Using fluorescent microscopy, it was revealed that Znt4 and Znt10 were located in the lysosome and Golgi, and Znt5 was located in the Golgi. Finally, we found that <em>znt4</em> knockdown reduced the zinc content of lysosome and Golgi in the control and zinc-treated group; <em>znt5</em> knockdown reduced the zinc content of Golgi in the control and zinc-treated group and <em>znt10</em> knockdown reduced the zinc content of Golgi in the zinc-treated group. High dietary zinc supplement up-regulated Znt4 and Znt5 protein expression. Above all, for the first time, we revealed that Klf4 and Nrf2 transcriptionally regulated the activities of <em>znt4</em> promoter; Mtf-1 and Atf4 transcriptionally regulated the activities of <em>znt5</em> promoter and Atf4 transcriptionally regulated the activities of <em>znt10</em> promoter, which provided innovative regulatory mechanism of zinc transporting in yellow catfish. Our study also elucidated their subcellular location, and regulatory role of zinc homeostasis in yellow catfish.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195041"},"PeriodicalIF":4.7,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916598","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":"Key interactions of RNA polymerase with 6S RNA and secondary channel factors during pRNA synthesis","authors":"Ivan Petushkov ,&nbsp;Daria Elkina ,&nbsp;Olga Burenina ,&nbsp;Elena Kubareva ,&nbsp;Andrey Kulbachinskiy","doi":"10.1016/j.bbagrm.2024.195032","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195032","url":null,"abstract":"<div><p>Small non-coding 6S RNA mimics DNA promoters and binds to the σ⁷⁰ holoenzyme of bacterial RNA polymerase (RNAP) to suppress transcription of various genes mainly during the stationary phase of cell growth or starvation. This inhibition can be relieved upon synthesis of short product RNA (pRNA) performed by RNAP from the 6S RNA template. Here, we have shown that pRNA synthesis depends on specific contacts of 6S RNA with RNAP and interactions of the σ finger with the RNA template in the active site of RNAP, and is also modulated by the secondary channel factors. We have adapted a molecular beacon assay with fluorescently labeled σ⁷⁰ to analyze 6S RNA release during pRNA synthesis. We found the kinetics of 6S RNA release to be oppositely affected by mutations in the σ finger and in the CRE pocket of core RNAP, similarly to the reported role of these regions in promoter-dependent transcription. Secondary channel factors, DksA and GreB, inhibit pRNA synthesis and 6S RNA release from RNAP, suggesting that they may contribute to the 6S RNA-mediated switch in transcription during stringent response. Our results demonstrate that pRNA synthesis depends on a similar set of contacts between RNAP and 6S RNA as in the case of promoter-dependent transcription initiation and reveal that both processes can be regulated by universal transcription factors acting on RNAP.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195032"},"PeriodicalIF":4.7,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825537","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":"A promoter-dependent upstream activator augments CFTR expression in diverse epithelial cell types","authors":"Giuliana C. Coatti,&nbsp;Nirbhayaditya Vaghela,&nbsp;Pulak Gillurkar,&nbsp;Shih-Hsing Leir,&nbsp;Ann Harris","doi":"10.1016/j.bbagrm.2024.195031","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195031","url":null,"abstract":"<div><p>The cystic fibrosis transmembrane conductance regulator (<em>CFTR</em>) gene encodes an anion-selective channel found in epithelial cell membranes. Mutations in <em>CFTR</em> cause cystic fibrosis (CF), an inherited disorder that impairs epithelial function in multiple organs. Most men with CF are infertile due to loss of intact genital ducts. Here we investigated a novel epididymis-selective <em>cis</em>-regulatory element (CRE), located within a peak of open chromatin at -9.5 kb 5′ to the <em>CFTR</em> gene promoter. Activation of the -9.5 kb CRE alone by CRISPRa had no impact on <em>CFTR</em> gene expression. However, CRISPRa co-activation of the -9.5 kb CRE and the <em>CFTR</em> gene promoter in epididymis cells significantly augmented CFTR mRNA and protein expression when compared to promoter activation alone. This increase was accompanied by enhanced chromatin accessibility at both sites. Furthermore, the combined CRISPRa strategy activated <em>CFTR</em> expression in other epithelial cells that lack open chromatin at the -9.5 kb site and in which the locus is normally inactive. However, the -9.5 kb CRE does not function as a classical enhancer of the <em>CFTR</em> promoter in transient reporter gene assays. These data provide a novel mechanism for activating/augmenting CFTR expression, which may have therapeutic utility for mutations that perturb <em>CFTR</em> transcription.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195031"},"PeriodicalIF":4.7,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874939924000270/pdfft?md5=e8ee5a0b32c65fe0747b2b7e3cfe1534&pid=1-s2.0-S1874939924000270-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825536","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":"TAT38 and TAT38 mimics potently inhibit adipogenesis by repressing C/EBPα, PPARγ, Pi-PPARγ, and SREBP1 expression","authors":"Sun-young Park ,&nbsp;Dongyoon Shin ,&nbsp;Young So Yoon ,&nbsp;Sujin Park ,&nbsp;Seung-Soon Im ,&nbsp;Yeongshin Kim ,&nbsp;Young-Soo Kim ,&nbsp;CheolSoo Choi ,&nbsp;Man-Wook Hur","doi":"10.1016/j.bbagrm.2024.195030","DOIUrl":"10.1016/j.bbagrm.2024.195030","url":null,"abstract":"<div><p>Antiretroviral therapy-naive people living with HIV possess less fat than people without HIV. Previously, we found that HIV-1 transactivator of transcription (TAT) decreases fat in <em>ob/ob</em> mice. The TAT38 (a.a. 20–57) is important in the inhibition of adipogenesis and contains three functional domains: Cys-ZF domain (a.a. 20–35 TACTNCYCAKCCFQVC), core-domain (a.a. 36–46, FITKALGISYG), and protein transduction domain (PTD)(a.a. 47–57, RAKRRQRRR). Interestingly, the TAT38 region interacts with the Cyclin T1 of the P-TEFb complex, of which expression increases during adipogenesis. The X-ray crystallographic structure of the complex showed that the Cys-ZF and the core domain bind to the Cyclin T1 via hydrophobic interactions. To prepare TAT38 mimics with structural and functional similarities to TAT38, we replaced the core domain with a hydrophobic aliphatic amino acid (from carbon numbers 5 to 8). The TAT38 mimics with 6-hexanoic amino acid (TAT38 Ahx (C6)) and 7-heptanoic amino acid (TAT38 Ahp (C7)) inhibited adipogenesis of 3T3-L1 potently, reduced cellular triglyceride content, and decreased body weight of diet-induced obese (DIO) mice by 10.4–11 % in two weeks. The TAT38 and the TAT38 mimics potently repressed the adipogenic transcription factors genes, C/EBPα, PPARγ, and SREBP1. Also, they inhibit the phosphorylation of PPARγ. The TAT peptides may be promising candidates for development into a drug against obesity or diabetes.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195030"},"PeriodicalIF":4.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760884","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":"Structural basis of the interaction between TFIIS and Leo1 from Arabidopsis thaliana","authors":"Yuzhu Wang ,&nbsp;Meng Chen ,&nbsp;Haoyu Ma ,&nbsp;Zhongliang Zhu ,&nbsp;Jie Gao ,&nbsp;Shanhui Liao ,&nbsp;Jiahai Zhang ,&nbsp;Xiaoming Tu","doi":"10.1016/j.bbagrm.2024.195027","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195027","url":null,"abstract":"","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195027"},"PeriodicalIF":4.7,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825535","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":"The nucleolus: Coordinating stress response and genomic stability","authors":"Katiuska González-Arzola","doi":"10.1016/j.bbagrm.2024.195029","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195029","url":null,"abstract":"<div><p>The perception that the nucleoli are merely the organelles where ribosome biogenesis occurs is challenged. Only around 30 % of nucleolar proteins are solely involved in producing ribosomes. Instead, the nucleolus plays a critical role in controlling protein trafficking during stress and, according to its dynamic nature, undergoes continuous protein exchange with nucleoplasm under various cellular stressors. Hence, the concept of nucleolar stress has evolved as cellular insults that disrupt the structure and function of the nucleolus. Considering the emerging role of this organelle in DNA repair and the fact that rDNAs are the most fragile genomic loci, therapies targeting the nucleoli are increasingly being developed. Besides, drugs that target ribosome synthesis and induce nucleolar stress can be used in cancer therapy. In contrast, agents that regulate nucleolar activity may be a potential treatment for neurodegeneration caused by abnormal protein accumulation in the nucleolus. Here, I explore the roles of nucleoli beyond their ribosomal functions, highlighting the factors triggering nucleolar stress and their impact on genomic stability.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195029"},"PeriodicalIF":4.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650468","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":"The role of nucleotide opening dynamics in facilitated target search by DNA-repair proteins","authors":"Sujeet Kumar Mishra ,&nbsp;Sangeeta ,&nbsp;Dieter W. Heermann ,&nbsp;Arnab Bhattacherjee","doi":"10.1016/j.bbagrm.2024.195026","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195026","url":null,"abstract":"<div><p>Preserving the genomic integrity stands a fundamental necessity, primarily achieved by the DNA repair proteins through their continuous patrolling on the DNA in search of lesions. However, comprehending how even a single base-pair lesion can be swiftly and specifically recognized amidst millions of base-pair sites remains a formidable challenge. In this study, we employ extensive molecular dynamics simulations using an appropriately tuned model of both protein and DNA to probe the underlying molecular principles. Our findings reveal that the dynamics of a non-canonical base generate an entropic signal that guides the one-dimensional search of a repair protein, thereby facilitating the recognition of the lesion site. The width of the funnel perfectly aligns with the one-dimensional diffusion length of DNA-binding proteins. The generic mechanism provides a physical basis for rapid recognition and specificity of DNA damage sensing and recognition.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195026"},"PeriodicalIF":4.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140631667","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":"The essential link: How STAT3 connects tumor metabolism to immunity","authors":"Shu Zhong,&nbsp;Jingjing Tong","doi":"10.1016/j.bbagrm.2024.195028","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195028","url":null,"abstract":"<div><p>Immunotherapy is a promising and long-lasting tumor treatment method, but it is challenged by the complex metabolism of tumors. To optimize immunotherapy, it is essential to further investigate the key proteins that regulate tumor metabolism and immune response. STAT3 plays a crucial role in regulating tumor dynamic metabolism and affecting immune cell function by responding to various cytokines and growth factors, which can be used as a potential target for immunotherapy. This review focuses on the crosstalk between STAT3 and tumor metabolism (including glucose, lipid, and amino acid metabolism) and its impact on the differentiation and function of immune cells such as T cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), and reveals potential treatment strategies.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195028"},"PeriodicalIF":4.7,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620880","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":"Illuminating ligand-induced dynamics in nuclear receptors through MD simulations","authors":"Tracy Yu ,&nbsp;Nishanti Sudhakar ,&nbsp;C. Denise Okafor","doi":"10.1016/j.bbagrm.2024.195025","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195025","url":null,"abstract":"<div><p>Nuclear receptors (NRs) regulate gene expression in critical physiological processes, with their functionality finely tuned by ligand-induced conformational changes. While NRs may sometimes undergo significant conformational motions in response to ligand-binding, these effects are more commonly subtle and challenging to study by traditional structural or biophysical methods. Molecular dynamics (MD) simulations are a powerful tool to bridge the gap between static protein-ligand structures and dynamical changes that govern NR function. Here, we summarize a handful of recent studies that apply MD simulations to study NRs. We present diverse methodologies for analyzing simulation data with a detailed examination of the information each method can yield. By delving into the strengths, limitations and unique contributions of these tools, this review provides guidance for extracting meaningful data from MD simulations to advance the goal of understanding the intricate mechanisms by which ligands orchestrate a range of functional outcomes in NRs.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195025"},"PeriodicalIF":4.7,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S187493992400021X/pdfft?md5=7d5eb13de1394345e0d37b70621dfa76&pid=1-s2.0-S187493992400021X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140607084","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":"Global control of RNA polymerase II","authors":"Alexander Gillis,&nbsp;Scott Berry","doi":"10.1016/j.bbagrm.2024.195024","DOIUrl":"10.1016/j.bbagrm.2024.195024","url":null,"abstract":"<div><p>RNA polymerase II (Pol II) is the multi-protein complex responsible for transcribing all protein-coding messenger RNA (mRNA). Most research on gene regulation is focused on the mechanisms controlling <em>which genes</em> are transcribed <em>when</em>, or on the mechanics of transcription. How global Pol II activity is determined receives comparatively less attention. Here, we follow the life of a Pol II molecule from ‘assembly of the complex’ to nuclear import, enzymatic activity, and degradation. We focus on how Pol II spends its time in the nucleus, and on the two-way relationship between Pol II abundance and activity in the context of homeostasis and global transcriptional changes.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195024"},"PeriodicalIF":4.7,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874939924000208/pdfft?md5=66407b36023b5a96807e0166eddceb5e&pid=1-s2.0-S1874939924000208-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327338","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}