Epigenetics & Chromatin最新文献

{"title":"DNMT3B promotes the progression of pheochromocytoma by mediating the hypermethylation of LRP1B promoter.","authors":"Min Sun, Yanrong Ma, Jing Wan, Bingli Zheng, Zhenfeng Shi, Jiuzhi Li","doi":"10.1186/s13072-025-00592-8","DOIUrl":"https://doi.org/10.1186/s13072-025-00592-8","url":null,"abstract":"<p><strong>Background: </strong>Pheochromocytoma (Pheo) represents a potential metastatic neuroendocrine tumor. As a tumor suppressor gene, LRP1B is involved in the regulation of tumor progression. However, the precise regulatory mechanism of LRP1B in Pheo remains elusive.</p><p><strong>Methods: </strong>RT-QPCR, western blot and immunohistochemistry (IHC) were used to identify the expression levels of DNMT3B and LRP1B. Biochemistry assays including luciferase and ChIP were utilized to detect the interaction between the methyltransferase DNMT3B and LRP1B promoter. LRP1B or DNMT3B were knock-down in Pheo cell line by shRNAs. Functional experiments including clonal formation, migration, and in vivo transplantation were performed to evaluate the regulation of LRP1B or DNMT3B on tumor growth.</p><p><strong>Results: </strong>LRP1B was down-regulated, while DNMT3B was up-regulated in Pheo.Overexpression of LRP1B or inhibition of DNMT3B inhibited the progress of Pheo. DNMT3B was responsible for the hypermethylation of LRP1B promoter in Pheo. At the same time, overexpression of DNMT3B reversed the inhibitory effect of overexpression of LRP1B on Pheo progression.</p><p><strong>Conclusion: </strong>DNMT3B mediated the hypermethylation of the tumor suppressive gene LRP1B and promotes Pheo progression.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"29"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LSD1 induces H3 K9 demethylation to promote adipogenesis in thyroid-associated ophthalmopathy.","authors":"Yuyan Xu, Jing Hu, Yuhang Fan, Licheng Sun, Ning Shen, Qihuang Jin, Ling Zhang, Jin Zhang, Fang Zhang, Hui Chen","doi":"10.1186/s13072-025-00586-6","DOIUrl":"https://doi.org/10.1186/s13072-025-00586-6","url":null,"abstract":"<p><strong>Background: </strong>Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disease influenced by multiple factors, including genetic and immune factors. The enlargement of orbital fat tissues are mainly due to abnormal activation of adipocyte differentiation. Epigenetic modifications provide mechanistic insight for regulating gene expression and cellular differentiation. Lysine specific demethylase 1 (LSD1) is reported in regulation of adipogenesis. Therefore, it is critical to investigate the relationship between epigenetic modifier LSD1 and histone modification level during TAO process.</p><p><strong>Results: </strong>In this study, combined with the clinic study and highthrough sequencing approach, our results revealed that the volume of orbital fat tissue was lower in TAO patients compared to non-TAO patients, whereas the number of adipocytes was higher in TAO patients compared to non-TAO patients, the expression level of adipocyte differentiation markers were higher in TAO samples. Consistently, at the cellular system, the expression level of adipogenic markers were higher in the TAO derived cells compared with the non-TAO cells. And we found LSD1 was highly expressed in TAO-derived cells. However, knocking down LSD1 decreased the expression of adipocyte markers. Mechanistically, LSD1 promoted adipocyte gene activation by demethylating H3K9me2 at the promoter regions. Finally, treatment with pargyline, an LSD1 inhibitor, inhibited adipogenesis in a dose-dependent manner, and the same inhibition of adipogenesis results were obtained with treatment with teprotumumab alone or combined with pargyline.</p><p><strong>Conclusions: </strong>Overall, our study indicates that epigenetic modifications were dysregulated in TAO process, and these data elucidated a novel mechanism of adipocyte differentiation during TAO progression and positioned LSD1 as a potential anti-adipogenesis target in TAO. Further understanding of the interaction betwen transcription factors and epigeneic modifiers or other histone modifications in TAO is essential for providing new perspectives in TAO mechanistic study and clinical intervention.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"28"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetylation modification of AIM2 by KAT2B suppresses the AKT/Wnt/β-catenin signaling pathway activation and inhibits breast cancer progression.","authors":"Yaqiong Li, Lingcheng Wang, Wei Wei Wangb, Wei Huang, Shengchun Liu","doi":"10.1186/s13072-025-00591-9","DOIUrl":"https://doi.org/10.1186/s13072-025-00591-9","url":null,"abstract":"<p><strong>Background: </strong>The development of breast cancer is known to be greatly influenced by epigenetic changes. The impact of histone acetyltransferase KAT2B on AIM2 and AKT/Wnt/β-catenin signaling have not been studied yet.</p><p><strong>Methods: </strong>In this study, clinical breast cancer tissue and para-cancer tissue samples were collected from 60 breast cancer patients, and correlations between AIM2 expression and pathological parameters were analyzed. Breast cancer cell lines were obtained for in vitro studies, and AIM2 overexpression or KAT2B knockdown models were constructed. The CCK8 and Edu assay were conducted to measure cell proliferation, and cell invasion was determined by Transwell analysis. For mRNA and protein expression measurement, RT-qPCR and western blotting were utilized, respectively. Co-immunoprecipitation was used to investigate the interaction between KAT2B and AIM2. Animal models were established using BALB/c-nu mice through subcutaneous injection with breast cancer cells transfected with AIM2 K90R mutant vectors. Expression of Ki-67, KAT2B and AIM2 AcK90 was measured using immunohistochemistry.</p><p><strong>Results: </strong>The clinical samples showed that AIM2 was downregulated in breast cancer tissues and was linked to lymph node metastases and advanced clinical stage. Subsequently, the in vitro studies found that AIM2 exerted a suppressive impact on the growth, spread, and invasion of breast cancer cells. We further demonstrated that KAT2B mediates acetylation of AIM2 at the lysine 90 residue, which suppresses cancer cell growth, invasion, and migration through inhibiting the AKT/Wnt/β-catenin axis. In animal models, we further confirmed that acetylation of AIM2 inhibited the stimulation of the AKT/Wnt/β-catenin axis, thereby suppressing breast cancer growth in vivo. Finally, we proved that the KAT2B and acetylation of AIM2 correlated with the prognosis of clinical breast cancer.</p><p><strong>Conclusion: </strong>Our study suggests that KAT2B-mediated acetylation of AIM2 can suppress the stimulation of the AKT/Wnt/β-catenin axis, consequently inhibiting breast carcinoma progression.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"27"},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H3K27me3 and the PRC1-H2AK119ub pathway cooperatively maintain heterochromatin and transcriptional silencing after the loss of H3K9 methylation.","authors":"Kei Fukuda, Chikako Shimura, Yoichi Shinkai","doi":"10.1186/s13072-025-00589-3","DOIUrl":"https://doi.org/10.1186/s13072-025-00589-3","url":null,"abstract":"<p><strong>Background: </strong>Heterochromatin is a fundamental component of eukaryotic chromosome architecture, crucial for genome stability and cell type-specific gene regulation. In mammalian nuclei, heterochromatin forms condensed B compartments, distinct from the transcriptionally active euchromatic A compartments. Histone H3 lysine 9 and lysine 27 trimethylation (H3K9me3 and H3K27me3) are two major epigenetic modifications that enrich constitutive and facultative heterochromatin, respectively. Previously, we found that the redistribution of H3K27me3 following the loss of H3K9 methylation contributes to heterochromatin maintenance, while the simultaneous loss of both H3K27me3 and H3K9 methylation induces heterochromatin decondensation in mouse embryonic fibroblasts. However, the spatial positioning of B compartments largely persists, suggesting additional mechanisms are involved.</p><p><strong>Results: </strong>In this study, we investigated the role of H2AK119 monoubiquitylation (uH2A), a repressive chromatin mark deposited by Polycomb Repressive Complex 1 (PRC1), in maintaining heterochromatin structure following the loss of H3K9 and H3K27 methylation. We observed that uH2A and H3K27me3 are independently enriched in B compartments after H3K9 methylation loss. Despite the absence of H3K9me3 and H3K27me3, uH2A remained localized and contributed to heterochromatin retention. These results suggest that PRC1-mediated uH2A functions independently and cooperatively with H3K27me3 to maintain heterochromatin organization originally created by H3K9 methylation.</p><p><strong>Conclusion: </strong>Our findings highlight a compensatory role for uH2A in preserving heterochromatin structure after the loss of other repressive chromatin modifications. The PRC1-uH2A pathway plays a critical role in maintaining the integrity of B compartments and suggests that heterochromatin architecture is supported by a network of redundant epigenetic mechanisms in mammalian cells.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"26"},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSH2 is not required for either maintenance of DNA methylation or repeat contraction at the FMR1 locus in fragile X syndrome or the FXN locus in Friedreich's ataxia.","authors":"Jessalyn Grant-Bier, Kathryn Ruppert, Bruce Hayward, Karen Usdin, Daman Kumari","doi":"10.1186/s13072-025-00588-4","DOIUrl":"https://doi.org/10.1186/s13072-025-00588-4","url":null,"abstract":"<p><strong>Background: </strong>Repeat-induced epigenetic changes are observed in many repeat expansion disorders (REDs). These changes result in transcriptional deficits and/or silencing of the associated gene. MSH2, a mismatch repair protein that is required for repeat expansion in the REDs, has been implicated in the maintenance of DNA methylation seen in the region upstream of the expanded CTG repeats at the DMPK locus in myotonic dystrophy type 1 (DM1). Here, we investigated the role of MSH2 in aberrant DNA methylation in two additional REDs, fragile X syndrome (FXS) that is caused by a CGG repeat expansion in the 5' untranslated region (UTR) of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, and Friedreich's ataxia (FRDA) that is caused by a GAA repeat expansion in intron 1 of the frataxin (FXN) gene.</p><p><strong>Results: </strong>In contrast to what is seen at the DMPK locus in DM1, loss of MSH2 did not decrease DNA methylation at the FMR1 promoter in FXS embryonic stem cells (ESCs) or increase FMR1 transcription. This difference was not due to the differences in the CpG density of the two loci as a decrease in DNA methylation was also not observed in a less CpG dense region upstream of the expanded GAA repeats in the FXN gene in MSH2 null induced pluripotent stem cells (iPSCs) derived from FRDA patient fibroblasts. Surprisingly, given previous reports, we found that FMR1 reactivation was associated with a high frequency of MSH2-independent CGG-repeat contractions that resulted a permanent loss of DNA methylation. MSH2-independent GAA-repeat contractions were also seen in FRDA cells.</p><p><strong>Conclusions: </strong>Our results suggest that there are mechanistic differences in the way that DNA methylation is maintained in the region upstream of expanded repeats among different REDs even though they share a similar mechanism of repeat expansion. The high frequency of transcription-induced MSH2-dependent and MSH2-independent contractions we have observed may contribute to the mosaicism that is frequently seen in carriers of FMR1 alleles with expanded CGG-repeat tracts. These contractions may reflect the underlying problems associated with transcription through the repeat. Given the recent interest in the therapeutic use of transcription-driven repeat contractions, our data may have interesting mechanistic, prognostic, and therapeutic implications.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"24"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation signatures of severe RSV infection in infants: evidence from non-invasive saliva samples.","authors":"Sara Pischedda, Alberto Gómez-Carballa, Jacobo Pardo-Seco, Sandra Viz-Lasheras, Alba Camino-Mera, Xabier Bello, María José Curras-Tuala, Irene Rivero-Calle, Ana I Dacosta-Urbieta, Federico Martinón-Torres, Antonio Salas","doi":"10.1186/s13072-025-00587-5","DOIUrl":"https://doi.org/10.1186/s13072-025-00587-5","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) poses significant morbidity and mortality risks in childhood, particularly for previously healthy infants admitted to hospitals lacking predisposing risk factors for severe disease. This study aimed to investigate the role of the host epigenome in RSV infection severity using non-invasive buccal swabs from sixteen hospitalized infants admitted to the hospital for RSV infection. Eight patients had severe symptoms, and eight had mild to moderate symptoms. For DNA methylation analyses, the Illumina EPIC BeadChip was used with DNA isolated from saliva samples. To evaluate the basal DNA methylation level of the identified biomarkers a cohort of healthy control children was used. Furthermore, DNA methylation levels of candidate genes were confirmed by pyrosequencing in both the discovery and validation cohorts of patients with mild to moderate symptoms.</p><p><strong>Results: </strong>A panel of differentially methylated positions (DMPs) distinguishing severe from mild to moderate symptoms in infants was identified. DMPs were determined using a threshold of an adjusted P-value (false discovery rate, FDR) < 0.01 and an absolute difference in DNA methylation (delta beta) > 0.10. Differentially methylated regions (DMRs) were identified in the ZBTB38 (implicated in asthma and pulmonary disease) and the TRIM6-TRM34 gene region (associated with viral infections). The differential DNA methylation of these genes was validated in an independent replication cohort. A weighted correlation network analysis emphasized the pivotal role of a module with RAB11FIP5 as the hub gene, known for its critical function in regulating viral infections.</p><p><strong>Conclusions: </strong>Oral mucosa methylation may play a role in determining the severity of RSV disease in infants.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"25"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H3F3A K27M mutations drive a repressive transcriptome by modulating chromatin accessibility independent of H3K27me3 in Diffuse Midline Glioma.","authors":"Suraj Bhattarai, Faruck L Hakkim, Charles A Day, Florina Grigore, Alyssa Langfald, Igor Entin, Edward H Hinchcliffe, James P Robinson","doi":"10.1186/s13072-025-00585-7","DOIUrl":"https://doi.org/10.1186/s13072-025-00585-7","url":null,"abstract":"<p><strong>Background: </strong>Heterozygous histone H3.3K27M mutation is a primary oncogenic driver of Diffuse Midline Glioma (DMG). H3.3K27M inhibits the Polycomb Repressive Complex 2 (PRC2) methyltransferase activity, leading to global reduction and redistribution of the repressive H3 lysine 27 tri-methylation (H3K27me3). This epigenomic rewiring is thought to promote gliomagenesis, but the precise role of K27M in gene regulation and tumorigenesis remains incompletely understood.</p><p><strong>Results: </strong>We established isogenic DMG patient-derived cell lines using CRISPR-Cas9 editing to create H3.3 wild-type (WT), H3.3K27M, and combinations with EZH2 and EZH1 co-deletion, thereby eliminating PRC2 function and H3K27me3. RNA-seq and ATAC-seq analysis revealed that K27M exerts a novel epigenetic effect independent of PRC2 inhibition. While PRC2 loss led to widespread gene induction including HOX gene clusters, and activation of biological pathways, K27M induced a balanced gene deregulation with an overall repressive effect on pathway activity. Genes uniquely affected by K27M, independent of PRC2 loss, showed concordant changes in chromatin accessibility, with upregulated genes becoming more accessible. Importantly, xenografts of H3.3K27M/EZH1/2 WT cells formed tumors, whereas /EZH1/2 knockout cells did not, demonstrating a PRC2-independent role of K27M in tumorigenesis.</p><p><strong>Conclusion: </strong>Our findings reveal that the H3.3K27M mutation alters chromatin accessibility and uniquely deregulates gene expression independent of H3K27 methylation loss. These PRC2-independent functions of K27M contribute to changes in biological pathway activity and are necessary for tumor development, highlighting novel mechanisms of K27M-driven gliomagenesis.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"23"},"PeriodicalIF":4.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin remodeling and cancer: the critical influence of the SWI/SNF complex.","authors":"Fengxiang Hao, Ying Zhang, Jiayi Hou, Bin Zhao","doi":"10.1186/s13072-025-00590-w","DOIUrl":"https://doi.org/10.1186/s13072-025-00590-w","url":null,"abstract":"<p><p>The SWI/SNF complex was first identified in yeast and named after studies of mutants critical for the mating-type switch (SWI) and sucrose non-fermenting (SNF) pathways.The SWI/SNF complex plays a pivotal role in regulating gene expression by altering chromatin structure to promote or suppress the expression of specific genes, maintain stem cell pluripotency, and participate in various biological processes. Mutations in the SWI/SNF complex are highly prevalent in various human cancers, significantly impacting tumor suppressive or oncogenic functions and influencing tumor initiation and progression. This review focuses on the mechanisms by which ARID1A/ARID1B, PBRM1, SMARCB1, and SMARCA2/SMARCA4 contribute to cancer, the immunoregulatory roles of the SWI/SNF complex, its involvement in DNA repair pathways, synthetic lethality, and applications in precision oncology.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"22"},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 chromatin remodelers regulating HIV-1 transcription: a target for small molecule inhibitors.","authors":"Yuan Ma, Chuan Li, Susana Valente","doi":"10.1186/s13072-025-00582-w","DOIUrl":"https://doi.org/10.1186/s13072-025-00582-w","url":null,"abstract":"<p><p>HIV-1 can establish a lifelong infection by incorporating its proviral DNA into the host genome. Once integrated, the virus can either remain dormant or start active transcription, a process governed by the HIV Tat protein, host transcription factors and the chromatin landscape at the integration site. Histone-modifying enzymes and chromatin-remodeling enzymes play crucial roles in regulating this chromatin environment. Chromatin remodelers, a group of ATP-dependent proteins, collaborate with host proteins and histone-modifying enzymes to restructure nucleosomes, facilitating DNA repair, replication, and transcription. Recent studies have highlighted the importance of chromatin remodelers in HIV-1 latency, spurring research focused on developing small molecule modulators that can either reactivate the virus for eradication approaches or induce long-term latency to prevent future reactivation. Research efforts have primarily centered on the SWI/SNF family, though much remains to be uncovered regarding other chromatin remodeling families. This review delves into the general functions and roles of each chromatin remodeling family in the context of HIV and discusses recent advances in small molecule development targeting chromatin remodelers and the HIV Tat protein, aiming to improve therapeutic approaches against HIV.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"21"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drosophila architectural proteins M1BP and Opbp cooperatively form the active promoter of a ribosomal protein gene.","authors":"Igor Osadchiy, Anastasia Umnova, Galina V Pokholkova, Anton Golovnin, Vladimir A Gvozdev, Igor F Zhimulev, Pavel Georgiev, Oksana Maksimenko","doi":"10.1186/s13072-025-00584-8","DOIUrl":"https://doi.org/10.1186/s13072-025-00584-8","url":null,"abstract":"<p><strong>Background: </strong>In Drosophila, architectural proteins are frequently found in promoters, including those of genes with extremely high expression levels, such as ribosomal protein genes (RPGs). The involvement of several of these proteins in gene regulation in Drosophila has been shown, but the exact mechanisms of their possible cooperative action have not been fully elucidated.</p><p><strong>Results: </strong>In this study we dissected the contribution of the architectural proteins Opbp and M1BP, which are co-localized at several RPG promoters near the transcription start site, to promoter functioning. We found that Opbp has two domains that directly interact with CP190, Putzig (Pzg), and Chromator (Chro) proteins, the cofactors which are required for the activation of housekeeping (hk) gene promoters. These domains have redundant functions in vivo and can tether the cofactors forming open chromatin regions when are artificially recruited to the \"closed\" chromatin. Additionally, we observed interactions between M1BP and the same cofactors. In the transgene assay, the transcription driven by the 192-bp part of Rpl27A RPG promoter is fully dependent on the presence of at least one Opbp or M1BP binding site and it is sufficient for the very high activity of this promoter integrated into the hk gene cluster and moderate expression outside the cluster, while presence of both sites even more facilitates transcription.</p><p><strong>Conclusions: </strong>This study demonstrates that different architectural proteins can work independently and in cooperation and fulfill partially redundant functions in the activation of RPG promoters.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"20"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}