Acta Naturae最新文献_第5页

LINE-1 Methylation Status in Multiple Sclerosis Patients Is Associated with Changes in Folate Metabolism. 多发性硬化症患者LINE-1甲基化状态与叶酸代谢变化相关

IF 2 4区生物学

Acta Naturae Pub Date : 2025-07-01 DOI: 10.32607/actanaturae.27579

E A Tsymbalova, E A Chernyavskaya, G N Bisaga, A Y Polushin, E I Lopatina, I N Abdurasulova, V I Lioudyno

{"title":"LINE-1 Methylation Status in Multiple Sclerosis Patients Is Associated with Changes in Folate Metabolism.","authors":"E A Tsymbalova, E A Chernyavskaya, G N Bisaga, A Y Polushin, E I Lopatina, I N Abdurasulova, V I Lioudyno","doi":"10.32607/actanaturae.27579","DOIUrl":"10.32607/actanaturae.27579","url":null,"abstract":"The disruption of epigenetic regulation and the development of abnormal DNA methylation patterns are crucial steps in the pathogenesis of neurodegenerative diseases. Methylation alterations in multiple sclerosis (MS) patients may contribute to the dysregulation of gene expression linked to the regulation of inflammation, myelin production, and the preservation of the integrity of the myelin sheath. The possibility that epigenetic alterations could be reversed provides a rationale for studying their mechanisms. In this study, we evaluated the methylation status of LINE-1 retrotransposons in the peripheral blood cells of patients with MS and healthy controls. In healthy individuals, LINE-1 methylation levels were observed to decrease with advancing age. MS patients exhibited a positive correlation between LINE-1 methylation and MS duration. The study indicates that the level of LINE-1 methylation is notably higher in progressive MS compared to the remitting type. LINE-1 methylation variations in MS patients were observed to be associated with the serum levels of homocysteine and vitamin B9, and dependent on the genotype for the C677T polymorphism of the MTHFR gene as well. The data obtained point to the contribution of the C677T polymorphism to the appearance of epigenetic disorders in MS development and suggest that hypermethylation may be mediated by disruptions in the folate metabolism that accompany MS.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"94-103"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Store-Operated Calcium Entry As an Important Mechanism of Tumor Adaptation to an Aggressive Microenvironment. 储存操作钙进入是肿瘤适应侵袭性微环境的重要机制。

IF 1.5 4区生物学

Acta Naturae Pub Date : 2025-07-01 DOI: 10.32607/actanaturae.27574

A Yu Skopin, E V Kaznacheyeva

{"title":"Store-Operated Calcium Entry As an Important Mechanism of Tumor Adaptation to an Aggressive Microenvironment.","authors":"A Yu Skopin, E V Kaznacheyeva","doi":"10.32607/actanaturae.27574","DOIUrl":"10.32607/actanaturae.27574","url":null,"abstract":"Calcium signaling ensures efficient cellular functioning; calcium homeostasis disruption leaves behind detrimental sequelae for the cell both under calcium excess and deficiency conditions. Malignant transformation is accompanied by significant alterations in the expression of the proteins critical for store-operated calcium entry, resulting in the dysregulation of calcium signaling. It is plausible that a remodeling of intracellular signal transduction pathways in cancer cells is required in order to accelerate metabolic processes, as well as fuel further tumor growth and invasion. Meanwhile, fine-tuning of calcium signaling is observed under both normal and pathological conditions. In this context, research into the changes accompanying signal transduction within the tumor microenvironment is a key aspect of the investigation of the role of calcium signaling in tumor development. Factors characteristic of the tumor microenvironment were shown to have a significant effect on the function of calcium channels and the proteins that regulate calcium signaling. Major, adverse microenvironmental factors, such as acidification, elevated levels of reactive oxygen species and hypoxia, have a bearing on the store-operated calcium entry. It is crucial to understand whether changes in the expression of the key SOCE components represent an adaptation to the microenvironment or a result of carcinogenesis.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"28-39"},"PeriodicalIF":1.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Targeted Nanoliposomes for the Delivery of Boronophenylalanine into HER2-Positive Cells. 靶向纳米脂质体将硼苯丙氨酸递送至her2阳性细胞。

IF 1.5 4区生物学

Acta Naturae Pub Date : 2025-07-01 DOI: 10.32607/actanaturae.27722

G M Proshkina, E I Shramova, A B Mirkasymov, I N Zavestovskaya, S M Deyev

{"title":"Targeted Nanoliposomes for the Delivery of Boronophenylalanine into HER2-Positive Cells.","authors":"G M Proshkina, E I Shramova, A B Mirkasymov, I N Zavestovskaya, S M Deyev","doi":"10.32607/actanaturae.27722","DOIUrl":"10.32607/actanaturae.27722","url":null,"abstract":"Boron neutron capture therapy (BNCT) is a rapidly developing field of radiation therapy for cancer that is based on the accumulation of the radiosensitive 10B isotope in cancer cells, followed by tumor irradiation with thermal neutrons. Widespread use of BNCT in clinical practice remains limited because of the poor accumulation of boron-containing (10B) drugs in the tumor or their high toxicity to the body. This study focuses on the engineering of tumor-specific liposomes loaded with 4-L-boronophenylalanine (4-L-10BPA) for application in boron neutron capture therapy. According to the spectrophotometry and ICP-mass spectroscopy data, the 4-L-10BPA-to-liposome molar ratio is ~ 120,000. Liposomal targeting of human epidermal growth factor receptor 2 (HER2) was determined by HER2-specific designed ankyrin repeat protein (DARPin)_9-29 on the outer surface of liposomes. DARPin-modified liposomes were found to bind to HER2-overexpressing cells and be effectively internalized into the cytoplasm. The ability of DARPin-functionalized liposomes to precision-deliver large quantities of 4-L-10BPA into cancer cells may open up new prospects for BNCT.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"88-93"},"PeriodicalIF":1.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

p2rx3 Knockout Mice Have Altered Energy Metabolism in Hippocampal Neurons. p2rx3基因敲除小鼠海马神经元能量代谢改变

IF 2 4区生物学

Acta Naturae Pub Date : 2025-07-01 DOI: 10.32607/actanaturae.27551

A S Zelentsova, M V Pokrovskii, E A Patrakhanov, V S Shmigerova, M Yu Skorkina, A V Deykin

{"title":"p2rx3 Knockout Mice Have Altered Energy Metabolism in Hippocampal Neurons.","authors":"A S Zelentsova, M V Pokrovskii, E A Patrakhanov, V S Shmigerova, M Yu Skorkina, A V Deykin","doi":"10.32607/actanaturae.27551","DOIUrl":"10.32607/actanaturae.27551","url":null,"abstract":"The hippocampus is a key component of the brain that is associated with the formation of longterm memory, the energy metabolism of neurons playing a pivotal role in its mechanisms. The P2X3 receptor in the hippocampus is considered an attractive target when searching for novel biologically active substances that could work to reduce anxiety, epileptic conditions, and improve cognitive functions. In this work, the intensity of mitochondrial respiration, the glycolytic capacity, and the energy phenotype of hippocampal neurons were studied in p2rx3 knockout mice. The p2rx3 knockout mice were engineered by genome editing using the CRISPR/Cas9 system. The primary mixed culture of hippocampal neurons was derived from two-day-old newborn mice with the p2rx3-/- and p2rx3+/- genotypes. Mitochondrial respiration was measured on a Seahorse Bioscience HS mini Cell Metabolism Analyzer (Agilent, USA) using the appropriate kits for the Mitostress test, glycotest, and energy phenotype assessment test. The transgenic mice with the p2rx3-/- genotype were characterized by an aerobic type of mitochondrial respiration, an increase in ATP production by 84.4% (p < 0.05), an increase in maximum respiration by 72.3% (p < 0.05), and a 36% (p < 0.05) increase in the respiratory reserve. Meanwhile, the spare respiratory capacity of mitochondria, the rate of glycolysis, and the glycolytic capacity in these mice were reduced by 36.6, 75.7 and 78.6% (p < 0.05), respectively. Our findings indicate that mitochondria work at close to maximum energy capacity. The p2rx3 knockout animals are a unique model for the search for pharmacological targets that can help correct the energy metabolism of brain cells and eliminate cognitive dysfunctions.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"49-55"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Test System for Studying Biotin Transport upon SLC5A6 Gene Inactivation. SLC5A6基因失活时生物素转运研究的测试系统

IF 2 4区生物学

Acta Naturae Pub Date : 2025-07-01 DOI: 10.32607/actanaturae.27645

A Yu Rudenko, P A Zotova, O A Averina, A V Priymak, M P Rubtsova, S S Mariasina, R M Ozhiganov, O A Dontsova, P V Sergiev

{"title":"Test System for Studying Biotin Transport upon SLC5A6 Gene Inactivation.","authors":"A Yu Rudenko, P A Zotova, O A Averina, A V Priymak, M P Rubtsova, S S Mariasina, R M Ozhiganov, O A Dontsova, P V Sergiev","doi":"10.32607/actanaturae.27645","DOIUrl":"10.32607/actanaturae.27645","url":null,"abstract":"This paper introduces a test system for the investigation of biotin transport following inactivation of the SLC5A6 gene, which encodes the sodium-dependent multivitamin transporter SLC5A6. The aim was to develop a method for assessing the efficiency of biotin penetration across the cell membrane following inactivation of the SLC5A6 gene and to explore the feasibility of delivering biotin derivatives into cells independent of SLC5A6. The test system is built upon modified HEK293 cell lines with overexpression of the BirA* biotin ligase, with the first line comprising a functional SLC5A6 gene and the second one involving an inactivated version of this gene mimicking impaired biotin transport. This test system was used to investigate the transport of biotin and its two derivatives, namely the biotin conjugate with p-aminophenylalanine (Bio-1) and biotin methyl ester (Bio-2), through the cell membrane. It has been determined that biotin and its methyl ester (Bio-2) can enter cells independently of the SLC5A6 transporter, which points to the presence of alternative transport pathways. The biotin derivative Bio-1, which contains p-aminophenylalanine, is internalized into cells solely through the hSMVT transporter. The novel test system will serve as a tool for investigating the pathways involved in vitamin entry into cells and for developing therapeutic strategies for individuals with mutations in the SLC5A6 gene, as well as other transport-related genes.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"119-129"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

RNA Interference of the Genes Associated with the Invasion of Brain Tumor Cells. 脑肿瘤细胞侵袭相关基因的RNA干扰。

IF 1.5 4区生物学

Acta Naturae Pub Date : 2025-07-01 DOI: 10.32607/actanaturae.27657

M A Dymova, O A Kartina, D V Drokov, E V Kuligina, V A Richter

{"title":"RNA Interference of the Genes Associated with the Invasion of Brain Tumor Cells.","authors":"M A Dymova, O A Kartina, D V Drokov, E V Kuligina, V A Richter","doi":"10.32607/actanaturae.27657","DOIUrl":"10.32607/actanaturae.27657","url":null,"abstract":"High-grade gliomas are among the most aggressive malignant pathologies of the brain. The high invasive potential of tumor cells causes relapses of the disease even after radical resection of the tumor. The signatures of the genes associated with the invasion of glioma cells have now been identified. The expression products of these genes are involved in various signaling pathways, such as cellular protein catabolism, the p53 signaling pathway, transcription dysregulation, and the JAK-STAT signaling pathway. Therefore, they can indirectly modulate the invasive potential of tumor cells. Using RNA interference technology, it is possible to change the expression level of the detected genes and reduce the invasive and proliferative potentials of cancer cells. This review focuses on the use of this technology to influence various links in signaling pathways and, accordingly, the cellular processes associated with the invasion of glioblastoma cells. Furthermore, the review discusses the problems associated with delivering interfering RNAs into cells and ways to solve them.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"18-27"},"PeriodicalIF":1.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Ortho- and Meta-monochlorinated Biphenyls Suppress Humoral Immunity and Exert Toxic Effects on Mouse Liver Cells. 邻、间一氯联苯抑制体液免疫并对小鼠肝细胞产生毒性作用。

IF 2 4区生物学

Acta Naturae Pub Date : 2025-07-01 DOI: 10.32607/actanaturae.27596

D O Egorova, S V Gein, N A Korolev, N P Loginova

{"title":"Ortho- and Meta-monochlorinated Biphenyls Suppress Humoral Immunity and Exert Toxic Effects on Mouse Liver Cells.","authors":"D O Egorova, S V Gein, N A Korolev, N P Loginova","doi":"10.32607/actanaturae.27596","DOIUrl":"10.32607/actanaturae.27596","url":null,"abstract":"Widespread environmental contamination with polychlorinated biphenyls (PCBs) leads to serious health problems for humans and animals. Our main focus should be on studying the negative effects of exposure to medium- and highly chlorinated PCBs in the human body. There is limited information on the impact of low-chlorinated biphenyls containing 1-2 substituents per molecule on the functions of mammalian organs and systems. Under natural conditions, PCBs can undergo bacterial degradation; the resulting compounds belong to a group of secondary pollutants and are considered hazardous to the environment. Because of limited research, the question regarding the impact of mono-substituted chlorobiphenyl congeners, as well as the products of their biotransformation, remains open. In the presented work, the effects of ortho- and meta- substituted monochlorinated biphenyls on the functions of immune system cells and the morphofunctional state of the liver of mammals in vivo are revealed for the first time. PCB 1 and PCB 2 were found to suppress humoral immunity and induce a productive inflammatory response, as well as widespread protein dystrophy with necrotic foci in the liver. The products of a aerobic bacterial transformation of PCB 1 and PCB 2 were shown to not have a negative effect on the mammalian immune system but proved toxic to hepatocytes, although to a lesser extent than the original chlorobiphenyls.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"40-43"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12560052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The Hypomethylating Agent 5-Azacitidine Potentiates the Effect of RAS and Sp1 Inhibitors in Neuroblastoma Cells. 低甲基化剂5-阿扎胞苷增强RAS和Sp1抑制剂在神经母细胞瘤细胞中的作用。

IF 1.5 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27558

K A Ivanenko, A V Snezhkina, M A Zolotovskaia, P V Spirin, O G Leonova, V I Popenko, A V Kudryavtseva, A A Buzdin, V S Prassolov, T D Lebedev

{"title":"The Hypomethylating Agent 5-Azacitidine Potentiates the Effect of RAS and Sp1 Inhibitors in Neuroblastoma Cells.","authors":"K A Ivanenko, A V Snezhkina, M A Zolotovskaia, P V Spirin, O G Leonova, V I Popenko, A V Kudryavtseva, A A Buzdin, V S Prassolov, T D Lebedev","doi":"10.32607/actanaturae.27558","DOIUrl":"10.32607/actanaturae.27558","url":null,"abstract":"Neuroblastoma is a malignant solid tumor caused by the transformation of neural crest cells. Neuroblastoma predominantly occurs in children and is associated with a poor prognosis. In this regard, the development of novel approaches to neuroblastoma treatment, including combination therapy, is relevant. DNA hypermethylation of neuroblastoma cells indicates that it is possible to use hypomethylating agents in a combination therapy of the disease. In order to identify effective combinations of antitumor drugs, we analyzed the transcriptomic changes that take place in neuroblastoma SH-SY5Y cells after treatment with the hypomethylating agent 5-azacitidine and then experimentally tested the effectiveness of these combinations. Mithramycin A and lonafarnib were the two drugs that, in combination with 5-azacitidine, appeared to exert a synergistic effect on SH-SY5Y cell death. These drugs inhibit the signaling pathway associated with the transcription factor Sp1 and RAS-MAPK signaling pathway, which are activated by 5-azacitidine. An analysis of the signaling pathways also revealed an activation of the signaling pathways associated with neuroblastoma cell differentiation, as well as apoptosis induction, as confirmed by multiplex and confocal microscopy. Hence, by analyzing the changes in the signaling pathways, the mechanisms of cell death and cell adaptation to hypomethylating agents can be understood, and this can be further used to develop novel therapeutic approaches to neuroblastoma therapy.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"86-97"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Classification and Quantification of Unproductive Splicing Events. 非生产性剪接事件的分类与量化。

IF 1.5 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27572

L G Zavileyskiy, E A Chernyavskaya, M A Vlasenok, D D Pervouchine

{"title":"Classification and Quantification of Unproductive Splicing Events.","authors":"L G Zavileyskiy, E A Chernyavskaya, M A Vlasenok, D D Pervouchine","doi":"10.32607/actanaturae.27572","DOIUrl":"10.32607/actanaturae.27572","url":null,"abstract":"In eukaryotic cells, the nonsense-mediated decay (NMD) pathway degrades mRNAs with premature stop codons. The coupling between NMD and alternative splicing (AS) generates NMD-sensitive transcripts (NMD targets, NMDTs) that play an important role in the gene expression regulation via the unproductive splicing mechanism. Understanding this mechanism requires proper identification of NMDT-generating AS events. Here, we developed NMDj, a tool for the identification, classification and quantification of NMDTgenerating AS events which does not rely on the best matching transcript partner principle employed by the existing methods. Instead, NMDj uses a set of characteristic introns that discriminate NMDTs from all protein-coding transcripts. The benchmark on simulated RNA-Seq data demonstrated that NMDj allows to quantify NMDT-generating AS events with better precision compared to other existing methods. NMDj represents a generic method suitable for the accurate classification of arbitrarily complex AS events that generate NMDTs. The NMDj pipeline is available through the repository https://github.com/zavilev/NMDj/.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"75-85"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Cis-regulatory Function of the Pou5f1 Gene Promoter in the Mouse MHC Locus. Pou5f1基因启动子在小鼠MHC位点的顺式调控功能。

IF 1.5 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27602

V V Ermakova, E V Aleksandrova, A A Kuzmin, A N Tomilin

{"title":"Cis-regulatory Function of the Pou5f1 Gene Promoter in the Mouse MHC Locus.","authors":"V V Ermakova, E V Aleksandrova, A A Kuzmin, A N Tomilin","doi":"10.32607/actanaturae.27602","DOIUrl":"10.32607/actanaturae.27602","url":null,"abstract":"The Pou5f1 gene encodes the Oct4 protein, one of the key transcription factors required for maintaining the pluripotent state of epiblast cells and the viability of germ cells. However, functional genetics provides convincing evidence that Pou5f1 has a broader range of functions in mouse ontogeny, including suppression of atherosclerotic processes. Related studies have primarily focused on the functions of the Oct4 protein, while the regulatory sequences within the Pou5f1 gene have not been considered. In this study, we have developed a genetic model which is based on mouse embryonic stem cells (ESCs) for assessing the roles of the Pou5f1 gene promoter in the transcriptional regulation of neighboring genes within the major histocompatibility complex (MHC) locus. We have demonstrated that deletion of this promoter affects the expression of selected genes within this locus neither in ESCs nor in the trophoblast derivatives of these cells. A notable exception is the Tcf19 gene, which is upregulated upon Pou5f1 promoter deletion and might be associated with the atherosclerosis pathology due to its pro-inflammatory activity. The developed genetic model will pave the way for future studies into the functional contribution of the cis-regulatory association of Pou5f1, Tcf19, and, possibly, other genes with the atherosclerotic phenotype previously reported for mice carrying the Pou5f1 promoter deletion in vascular endothelial and smooth muscle cells.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"64-74"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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