Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

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The crucial role of small heat shock proteins in prostate cancer: mechanisms and new therapeutic perspectives 小热休克蛋白在前列腺癌中的关键作用:机制和新的治疗前景
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-04-11 DOI: 10.1016/j.bbagrm.2025.195090
Yuankang Feng , Jialu Ma , Zhihao Bo , Dan Yue , Yong Wang
{"title":"The crucial role of small heat shock proteins in prostate cancer: mechanisms and new therapeutic perspectives","authors":"Yuankang Feng ,&nbsp;Jialu Ma ,&nbsp;Zhihao Bo ,&nbsp;Dan Yue ,&nbsp;Yong Wang","doi":"10.1016/j.bbagrm.2025.195090","DOIUrl":"10.1016/j.bbagrm.2025.195090","url":null,"abstract":"<div><div>As resistance to new anti-androgen drugs occurs more frequently, increasing numbers of researchers are exploring alternative key molecular targets for prostate cancer treatment. The small heat shock protein (sHSP) family is a subclass of heat shock proteins (HSPs). Due to the smaller molecular size of their monomers, they often function as large oligomeric complexes with diverse biological roles, thus garnering increasing attention from urologists. Different members of the sHSP family exhibit distinct biological roles in prostate cancer, offering a new perspective for precision therapy. In this review, we summarize the specific roles of sHSP family members in prostate cancer and analyze their similarities and differences. Additionally, we discuss and review the drugs targeting various sHSPs in prostate cancer, providing new insights into the exploration and further application of sHSP-targeted therapies.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 2","pages":"Article 195090"},"PeriodicalIF":2.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839013","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}
引用次数: 0
Genome-wide screening reveals repression by nuclear exosome as a prerequisite for intron-mediated enhancement in Saccharomyces cerevisiae 全基因组筛选显示核外泌体的抑制是酿酒酵母内含子介导的增强的先决条件
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-04-10 DOI: 10.1016/j.bbagrm.2025.195089
Hiroki Kikuta , Shunya Takeda , Rinji Akada , Hisashi Hoshida
{"title":"Genome-wide screening reveals repression by nuclear exosome as a prerequisite for intron-mediated enhancement in Saccharomyces cerevisiae","authors":"Hiroki Kikuta ,&nbsp;Shunya Takeda ,&nbsp;Rinji Akada ,&nbsp;Hisashi Hoshida","doi":"10.1016/j.bbagrm.2025.195089","DOIUrl":"10.1016/j.bbagrm.2025.195089","url":null,"abstract":"<div><div>Introns can enhance gene expression, a phenomenon called intron-mediated enhancement (IME). Previously proposed IME mechanisms do not sufficiently explain the variability in enhancement levels, suggesting that IME mechanism has not been fully understood. A comprehensive screening of genes involved in IME can provide valuable insights. Recently, using a luciferase coding sequence (yCLuc), we showed that IME functions by relieving repression rather than simply enhancing expression. The expression of yCLuc is repressed by the specific nucleotide sequence UCUU, and adding an intron relieves this repression in the yeast <em>Saccharomyces cerevisiae</em>. Herein, genome-wide screenings were conducted using <em>S. cerevisiae</em> knockout strain libraries to identify genes involved in IME. For screening, yCLuc was expressed with and without an intron in knockout strains. Consequently, <em>CDC73</em>, a regulator of RNA polymerase II (RNAPII), was identified as essential for enhancement. Additionally, 23 genes specifically involved in the repression were identified. These 23 genes are related to nuclear exosomes, RNA modification, RNAPII regulation, the nuclear pore complex, ribosomes, and chromatin modification. Among these, genes associated with nuclear exosomes, which degrade various RNAs in the nucleus, showed the largest impact on expression. The RNA sequence UCUU has been reported as a target for RNA degradation by nuclear exosomes. These findings suggested that UCUU-containing coding sequences are primarily repressed via RNA degradation by the nuclear exosome through UCUU recognition, with this repression being relieved by the presence of an intron.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 2","pages":"Article 195089"},"PeriodicalIF":2.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851848","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}
引用次数: 0
Specific DNA features of the RNA polymerase I core promoter element targeted by core factor 核心因子所针对的 RNA 聚合酶 I 核心启动子元件的特定 DNA 特征
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-04-09 DOI: 10.1016/j.bbagrm.2025.195088
Nathan J. Munoff, Brian J. Zeberl, Matthew A. Palmer, Wayne A. Decatur, Bridget M. Walker, Jyoti D. Adala, Zsuzsa K. Szemere, Aula M. Fakhouri, Bruce A. Knutson
{"title":"Specific DNA features of the RNA polymerase I core promoter element targeted by core factor","authors":"Nathan J. Munoff,&nbsp;Brian J. Zeberl,&nbsp;Matthew A. Palmer,&nbsp;Wayne A. Decatur,&nbsp;Bridget M. Walker,&nbsp;Jyoti D. Adala,&nbsp;Zsuzsa K. Szemere,&nbsp;Aula M. Fakhouri,&nbsp;Bruce A. Knutson","doi":"10.1016/j.bbagrm.2025.195088","DOIUrl":"10.1016/j.bbagrm.2025.195088","url":null,"abstract":"<div><div>RNA polymerase I (Pol I) is essential for ribosomal RNA (rRNA) synthesis, driving ribosome biogenesis in eukaryotes. Transcription initiation by Pol I requires core factor (CF) binding to the core element (CE) of the ribosomal DNA (rDNA) promoter. Despite structural conservation across species, significant sequence variability suggests CF recognizes DNA through structural features rather than specific sequences. We investigated CF's DNA binding preferences to elucidate the role of DNA structural properties in CE recognition. Analysis of CE sequences from 35 fungal species revealed conserved structural features, notably a rigid AT-rich patch at positions −22 to −20 and a conserved G base pair at position −24. Competition-based electrophoretic mobility shift assays (EMSA) with single base-pair substitutions showed CF tolerates mutations at many positions but is sensitive to changes in the AT-rich patch. Loss of CF binding correlated with alterations in DNA structural properties such as increased bendability, decreased curvature, widened minor groove width, and altered helix twist. In vitro SELEX experiments identified novel CE sequences preferentially bound by CF, exhibiting increased GC content, higher bendability, and decreased curvature despite lacking sequence conservation. Classification based on bendability profiles revealed CF preferentially binds bendable sequences. In vivo selection assays confirmed these findings, demonstrating consistent CF binding preferences within a cellular context. Our results indicate that CF recognizes and binds to the CE primarily through specific DNA structural features rather than nucleotide sequences. Structural properties like bendability, curvature, and minor groove width are critical determinants of CF binding, facilitating effective Pol I transcription initiation.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 2","pages":"Article 195088"},"PeriodicalIF":2.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843295","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}
引用次数: 0
Hypoxia inducible factor HIF1α elevates expression of mRNA capping enzyme during cobalt chloride-induced hypoxia 缺氧诱导因子HIF1α在氯化钴诱导的缺氧过程中升高mRNA capping酶的表达。
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-04-05 DOI: 10.1016/j.bbagrm.2025.195087
Safirul Islam, Chandrama Mukherjee
{"title":"Hypoxia inducible factor HIF1α elevates expression of mRNA capping enzyme during cobalt chloride-induced hypoxia","authors":"Safirul Islam,&nbsp;Chandrama Mukherjee","doi":"10.1016/j.bbagrm.2025.195087","DOIUrl":"10.1016/j.bbagrm.2025.195087","url":null,"abstract":"<div><div>In response to hypoxia, hypoxia-inducible factors (HIFs) control the transcriptomic output to mitigate the hypoxic stress. Long noncoding RNAs (lncRNA) are found to be very crucial in regulating hypoxia. Like mRNAs, lncRNAs are protected by 5′ caps that are added by mRNA capping enzyme (CE) in the nucleus. The previous concept that capping takes place in the nucleus was changed by the recognition of a cytoplasmic pool of capping enzyme (cCE). cCE has been shown to recap its substrate uncapped mRNAs or long noncoding RNAs (lncRNAs) present in the cytoplasm, preventing their degradation, even during arsenite-induced oxidative stress. In this study, we examined the effect of CoCl<sub>2</sub> induced hypoxia on cCE and its function in regulating the substrate lncRNAs.</div><div>Here, we show that CoCl<sub>2</sub> induced hypoxia elevates the expressions of nuclear and cytoplasmic CE in HIF1α dependent manner as evidenced by Chromatin immunoprecipitation and HIF1α inhibitor experiments. Furthermore, we found cCE post-transcriptionally controls the stability of its target lncRNAs amidst CoCl<sub>2</sub> induced hypoxia. These results suggest that cCE, upregulated by HIF1α, may act as a posttranscriptional modulator for a few cCE-targeted lncRNAs.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 2","pages":"Article 195087"},"PeriodicalIF":2.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796384","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}
引用次数: 0
Transcription factors associated with regulation of transcriptome in human thigh and calf muscles at baseline and after six days of disuse
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-02-19 DOI: 10.1016/j.bbagrm.2025.195086
Anna A. Borzykh , Pavel A. Makhnovskii , Ivan I. Ponomarev, Tatiana F. Vepkhvadze, Egor M. Lednev, Ilya V. Rukavishnikov, Oleg I. Orlov, Elena S. Tomilovskaya, Daniil V. Popov
{"title":"Transcription factors associated with regulation of transcriptome in human thigh and calf muscles at baseline and after six days of disuse","authors":"Anna A. Borzykh ,&nbsp;Pavel A. Makhnovskii ,&nbsp;Ivan I. Ponomarev,&nbsp;Tatiana F. Vepkhvadze,&nbsp;Egor M. Lednev,&nbsp;Ilya V. Rukavishnikov,&nbsp;Oleg I. Orlov,&nbsp;Elena S. Tomilovskaya,&nbsp;Daniil V. Popov","doi":"10.1016/j.bbagrm.2025.195086","DOIUrl":"10.1016/j.bbagrm.2025.195086","url":null,"abstract":"<div><div>Disuse has a negative impact on the postural muscles of the trunk and legs. Different leg muscles demonstrate a differentiated and conservative response to disuse, in terms of a decrease in muscle mass, strength, aerobic performance, and changes in gene expression. We aimed to identify transcription factors regulating gene expression at baseline and after disuse in human <em>m. soleus</em> – a “slow” muscle with a strong postural function, and “mixed” <em>m. vastus lateralis</em>. Biopsies were taken from these muscles prior to and after 6 days of strict disuse (dry immersion). The enriched transcription factor binding sites (and corresponding factors) in the individual promoter regions of co-expressed genes were examined using the positional weight matrix approach. The baseline transcriptomic profiles and the disuse-induced changes (RNA-seq) differ significantly between muscles. In particular, the specific and significant response to disuse in <em>m. soleus</em> was found to be strongly related to the suppression of genes regulating the mitochondrial energy metabolism, the activation of the inflammatory response and the ubiquitin-proteasome system. This response is associated with the proinflammatory transcription factors such as families IRF, STAT, and other. The validity of approximately two-thirds of the predicted transcription factors was indirectly confirmed by the analysis of their function described in the literature. These identified transcription factors appear to be promising candidates for future targeted studies that mechanistically investigate gene expression regulation in various muscles at baseline, following disuse or inactivity.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 2","pages":"Article 195086"},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470039","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}
引用次数: 0
UPS regulation of gene expression and genome integrity
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-01-30 DOI: 10.1016/j.bbagrm.2025.195078
Sukesh R. Bhaumik
{"title":"UPS regulation of gene expression and genome integrity","authors":"Sukesh R. Bhaumik","doi":"10.1016/j.bbagrm.2025.195078","DOIUrl":"10.1016/j.bbagrm.2025.195078","url":null,"abstract":"","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 1","pages":"Article 195078"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076643","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}
引用次数: 0
TAP-MS analysis of FACT interactions and regulation by a ubiquitin ligase, San1
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-01-22 DOI: 10.1016/j.bbagrm.2025.195077
Priyanka Barman, Pritam Chakraborty, Shalini Guha, Amala Kaja, Rhea Bhaumik, Sukesh R. Bhaumik
{"title":"TAP-MS analysis of FACT interactions and regulation by a ubiquitin ligase, San1","authors":"Priyanka Barman,&nbsp;Pritam Chakraborty,&nbsp;Shalini Guha,&nbsp;Amala Kaja,&nbsp;Rhea Bhaumik,&nbsp;Sukesh R. Bhaumik","doi":"10.1016/j.bbagrm.2025.195077","DOIUrl":"10.1016/j.bbagrm.2025.195077","url":null,"abstract":"<div><div>An evolutionarily conserved heterodimeric FACT (<u>Fa</u>cilitates <u>c</u>hromatin <u>t</u>ranscription) regulates transcription, DNA repair, replication and other cellular processes via its interactions with other proteins. FACT is recently found to be regulated via ubiquitylation and 26S proteasomal degradation, alteration of which is associated with aberrant transcription and genome integrity. However, there has not been a systematic study to analyze FACT interactions proteome-wide in the presence and absence of its UPS (<u>U</u>biquitin-<u>p</u>roteasome <u>s</u>ystem) regulation, which could reveal new FACT interactors with mechanistic and functional implications. Here, we have adopted a proteome-wide approach via TAP (<u>T</u>andem <u>a</u>ffinity <u>p</u>urification)-mediated pull-down of FACT and its interactors from the soluble and insoluble cellular fractions followed by MS (<u>M</u>ass-<u>s</u>pectrometry) analysis. We find distinct interactors of FACT in the soluble and insoluble fractions in addition to a common set in both. While a set of all these interactors overlaps with previously known FACT partners, many are new, which are involved in different cellular processes such as transcription, DNA repair and chromatin regulation. Further, an intrinsically disordered ubiquitin ligase, San1, that ubiquitylates the Spt16 component of FACT for proteasomal degradation to regulate chromatin, transcription and genome integrity is found to influence the interactions of FACT with a set of proteins including epigenetic, transcription and DNA repair factors. Collectively, our results unveil proteome-wide FACT interactions and regulation by a ubiquitin ligase, hence shedding much light on FACT networks with functional and mechanistic implications.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 1","pages":"Article 195077"},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043436","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}
引用次数: 0
Susceptibility to pseudoexfoliation linked to intronic variant rs4926246 in CACNA1A: Evidence from an Indian population study CACNA1A基因内含子变异rs4926246对假脱落的易感性:来自印度人群研究的证据
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-01-16 DOI: 10.1016/j.bbagrm.2025.195076
Bushra Hayat , Swagatika Panigrahi , Senjit Ram Behera , Pranjya Paramita Mohanty , Debasmita Pankaj Alone
{"title":"Susceptibility to pseudoexfoliation linked to intronic variant rs4926246 in CACNA1A: Evidence from an Indian population study","authors":"Bushra Hayat ,&nbsp;Swagatika Panigrahi ,&nbsp;Senjit Ram Behera ,&nbsp;Pranjya Paramita Mohanty ,&nbsp;Debasmita Pankaj Alone","doi":"10.1016/j.bbagrm.2025.195076","DOIUrl":"10.1016/j.bbagrm.2025.195076","url":null,"abstract":"<div><div>Pseudoexfoliation (PEX) is an age-related, complex systemic disorder of protein aggregopathy. It is characterized by the extracellular fibril depositions, termed PEX fibrils, initially observed in various organ tissues during pseudoexfoliation syndrome (PEXS) and with significant prominence in the eye during advanced pseudoexfoliation glaucoma (PEXG). The study explores the association between <em>CACNA1A</em> (calcium channel, voltage-dependent, P/Q type, alpha 1 A subunit) variants and PEX in an Indian population. The investigation involved genotyping one intronic single nucleotide polymorphism (SNP), rs4926244, and three tag SNPs using the Sanger and TaqMan genotyping approaches in a cohort of 300 controls and 300 PEX patients (including 200 PEXS and 100 PEXG cases). Findings from the present study revealed a significant association at both allelic and genotypic levels for rs4926246, whereas rs4926244 showed association only at the genotypic level with PEX. Functional assays demonstrated increased mRNA expression linked to the risk genotype of both variants and luciferase reporter assays indicated an allele-specific regulatory effect of rs4926246.While in silico analysis predicted potential transcription factor binding sites for c-Myc and Hypoxia-inducing factor-1 (HIF-1) at the rs4926246 locus, electrophoretic mobility shift assay (EMSA) validated that only the “T” variant showed the reduced binding affinity with c-Myc compared to the protective variant “C”. Our study identifies rs4926246, an intronic variant strongly associated with both PEXS and PEXG, potentially influencing gene expression and protein binding, warranting further investigation into its role in PEX pathogenesis.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 1","pages":"Article 195076"},"PeriodicalIF":2.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016940","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}
引用次数: 0
Transcriptional responses of three slc39a/zip members (zip4, zip5 and zip9) and their roles in Zn metabolism in grass carp (Ctenopharyngodon idella) slc39a/zip三个成员zip4、zip5和zip9的转录响应及其在草鱼锌代谢中的作用
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-12-13 DOI: 10.1016/j.bbagrm.2024.195075
Jia-Cheng Guo , Peng-Cheng Xu , Yi-Chuang Xu , Tian-Hua Zhang , Lu-Lu Liu , Tao Liu , Zhi Luo
{"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 ,&nbsp;Peng-Cheng Xu ,&nbsp;Yi-Chuang Xu ,&nbsp;Tian-Hua Zhang ,&nbsp;Lu-Lu Liu ,&nbsp;Tao Liu ,&nbsp;Zhi Luo","doi":"10.1016/j.bbagrm.2024.195075","DOIUrl":"10.1016/j.bbagrm.2024.195075","url":null,"abstract":"<div><div>In order to explore the regulatory mechanism of <em>zip4</em>, <em>zip5</em> and <em>zip9</em> in zinc metabolism of grass carp (<em>Ctenopharyngodon idella</em>), the effects of zinc (Zn) on the mRNA expression of <em>zip4</em>, <em>zip5</em> and <em>zip9</em> were investigated. Compared to the control, the mRNA levels of <em>zip4</em> and <em>zip9</em> were significantly reduced under low and high zinc in L8824 cells; the mRNA expression level of <em>zip5</em> 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 <em>zip4</em>, <em>zip5</em> and <em>zip9</em> 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 <em>zip5</em> promoter and at −1679/−1689 bp of <em>zip9</em> promoter. Similarly, krüppel-like factor 4 (KLF4) could specifically bind to the −599/−609 bp sequence on the <em>zip5</em> promoter and the −261/−272 bp sequence on the <em>zip9</em> promoter. The results of electrophoretic mobility-shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) indicated that Zn incubation increased DNA binding capacity of STAT3 to <em>zip5</em> and <em>zip9</em> promoters, and decreased DNA binding capacity of KLF4 to <em>zip5</em> and <em>zip9</em> promoters. This study provides a good basis for elucidating the regulatory mechanism of zinc metabolism in the vertebrates.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 1","pages":"Article 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}
引用次数: 0
Experimental approaches to investigate biophysical interactions between homeodomain transcription factors and DNA 研究同源域转录因子与DNA之间生物物理相互作用的实验方法。
IF 2.6 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-12-05 DOI: 10.1016/j.bbagrm.2024.195074
Fadwa Mekkaoui , Robert A. Drewell , Jacqueline M. Dresch , Donald E. Spratt
{"title":"Experimental approaches to investigate biophysical interactions between homeodomain transcription factors and DNA","authors":"Fadwa Mekkaoui ,&nbsp;Robert A. Drewell ,&nbsp;Jacqueline M. Dresch ,&nbsp;Donald E. Spratt","doi":"10.1016/j.bbagrm.2024.195074","DOIUrl":"10.1016/j.bbagrm.2024.195074","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 1","pages":"Article 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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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