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Regulatory T cells in skin utilize the Cxcr4-Cxcl12 axis to promote hair follicle regeneration. 皮肤中的调节性T细胞利用Cxcr4-Cxcl12轴促进毛囊再生。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-22 DOI: 10.1016/j.celrep.2025.116467
Jarish N Cohen, Gayatri Kolluri, Sean Clancy, Victoire Gouirand, Courtney E Macon, Lokesh A Kalekar, Michael D Rosenblum
{"title":"Regulatory T cells in skin utilize the Cxcr4-Cxcl12 axis to promote hair follicle regeneration.","authors":"Jarish N Cohen, Gayatri Kolluri, Sean Clancy, Victoire Gouirand, Courtney E Macon, Lokesh A Kalekar, Michael D Rosenblum","doi":"10.1016/j.celrep.2025.116467","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116467","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) play important immunosuppressive and tissue-regenerative functions in skin. A subset of Tregs localizes to hair follicles (HFs), where they promote hair growth through activation of HF stem cells. However, the mechanisms driving Treg accumulation in HFs remain to be identified. We find that Tregs utilize Cxcr4 to accumulate in HF epithelium and that its expression is partially dependent on glucocorticoid receptor signaling. Additionally, we show that Cxcl12, the main cognate ligand of Cxcr4, is enriched in keratinocytes of the upper HF and that disruption of the Cxcr4-Cxcl12 axis results in suboptimal hair growth. Finally, we demonstrate that upper HF keratinocytes in human skin express Cxcr4 ligands in a pattern similar to that in murine skin. Collectively, these results reveal an evolutionary conserved pathway of Treg trafficking within a barrier tissue that promotes hair regeneration, which may have implications for immunotherapeutic modulation of human alopecia.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 11","pages":"116467"},"PeriodicalIF":6.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Muscle spindles provide flexible sensory feedback for movement sequences. 肌肉纺锤体为运动序列提供灵活的感觉反馈。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-22 DOI: 10.1016/j.celrep.2025.116452
William P Olson, Varun B Chokshi, Jeong Jun Kim, Noah J Cowan, Daniel H O'Connor
{"title":"Muscle spindles provide flexible sensory feedback for movement sequences.","authors":"William P Olson, Varun B Chokshi, Jeong Jun Kim, Noah J Cowan, Daniel H O'Connor","doi":"10.1016/j.celrep.2025.116452","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116452","url":null,"abstract":"<p><p>Sensory feedback is essential for motor performance and must adapt to task demands. Muscle spindle afferents (MSAs) are a major primary source of feedback about movement. Their responses are readily modulated online by fusimotor neurons and, in the unique case of jaw MSAs whose cell bodies lie within the central nervous system, by central synaptic inputs. They are, therefore, a powerful site for implementing flexible sensorimotor control. We record from MSAs innervating the jaw musculature of mice performing a directed lick sequence task. Jaw MSAs encode complex jaw-tongue kinematics. However, kinematic encoding alone accounts for less than half of jaw MSA spiking variability. Jaw MSA coding of kinematics changes based on sequence progression (beginning, middle, or end of the sequence or reward consumption), suggesting that jaw MSAs are flexibly tuned across the task. Dynamic modulation of feedback signals from jaw MSAs may shape sensorimotor control during complex behavior.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 11","pages":"116452"},"PeriodicalIF":6.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Integrating mutation, copy number, and gene expression data to identify driver genes of recurrent chromosome-arm losses. 整合突变,拷贝数和基因表达数据,以确定复发性染色体臂丢失的驱动基因。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-22 DOI: 10.1016/j.celrep.2025.116455
Ron Saad, Ron Shamir, Uri Ben-David
{"title":"Integrating mutation, copy number, and gene expression data to identify driver genes of recurrent chromosome-arm losses.","authors":"Ron Saad, Ron Shamir, Uri Ben-David","doi":"10.1016/j.celrep.2025.116455","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116455","url":null,"abstract":"<p><p>Aneuploidy is a hallmark of cancer, yet the genes driving recurrent chromosome-arm losses remain largely unknown. We present a systematic framework integrating mutation, copy number, and gene expression data to identify candidate driver genes of cancer type-specific recurrent chromosome-arm losses across 20 cancer types, using ∼7,500 tumors from The Cancer Genome Atlas. By analyzing focal deletions and point mutations that co-occur, or are mutually exclusive, with chromosome-arm losses, we pinpoint 322 candidate drivers associated with 159 recurring events. Our approach identifies known aneuploidy drivers such as TP53 and PTEN, while revealing multiple additional candidates, including tumor suppressors not previously linked to aneuploidy. We leverage expression changes associated with chromosome-arm losses to propose cancer-promoting pathway-level alterations. Integrating these findings highlights key candidate drivers that underlie the observed expression alterations, reinforcing their biological relevance. We provide a comprehensive catalog of candidate driver genes for recurrently lost chromosome-arms in human cancer.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 11","pages":"116455"},"PeriodicalIF":6.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Metabolic regulation of immunity in the tumor microenvironment. 肿瘤微环境中免疫的代谢调节。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-22 DOI: 10.1016/j.celrep.2025.116463
Shen Li, Yu Zhang, Huan Tong, Haozhen Sun, Hu Liao, Qingfang Li, Xuelei Ma
{"title":"Metabolic regulation of immunity in the tumor microenvironment.","authors":"Shen Li, Yu Zhang, Huan Tong, Haozhen Sun, Hu Liao, Qingfang Li, Xuelei Ma","doi":"10.1016/j.celrep.2025.116463","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116463","url":null,"abstract":"<p><p>Metabolic-immune crosstalk in the tumor microenvironment (TME) is a critical driver of tumorigenesis, progression, and immune evasion. Tumor cells undergo profound metabolic reprogramming, causing nutrient competition, toxic metabolite accumulation, and the formation of cold niches that gradually exhaust effector immune cells. In contrast, immunosuppressive cells exhibit strong metabolic adaptability, reinforcing the suppressive milieu. Moreover, tertiary lymphoid structures provide nutrient- and oxygen-rich \"moats\" that sustain the functions of B and T cells. In addition, metabolic-immune interactions establish novel checkpoints through an \"enzyme-metabolite-receptor\" axis, which synergize with PD-1/CTLA-4 pathways to promote resistance to immune checkpoint inhibitors (ICIs). Although monotherapies with metabolic inhibitors have shown limited efficacy, their combination with ICIs is promising. Therefore, this review discusses the field from three perspectives: metabolic stress in the TME, immune cell adaptation, and targeting metabolic immune checkpoints in combination with immunotherapy.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 11","pages":"116463"},"PeriodicalIF":6.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Non-conjugative plasmids limit their mobility to persist in nature. 非共轭质粒限制了它们在自然界中的迁移能力。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-22 DOI: 10.1016/j.celrep.2025.116456
Akshay Sabnis, Wendy Figueroa, Alfonso Santos-López, Jonathan Bradshaw, Melissa-Jane Chu Yuan Kee, John Chen, Álvaro San Millán, José R Penadés
{"title":"Non-conjugative plasmids limit their mobility to persist in nature.","authors":"Akshay Sabnis, Wendy Figueroa, Alfonso Santos-López, Jonathan Bradshaw, Melissa-Jane Chu Yuan Kee, John Chen, Álvaro San Millán, José R Penadés","doi":"10.1016/j.celrep.2025.116456","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116456","url":null,"abstract":"<p><p>Plasmids are mobile genetic elements that disseminate beneficial genes, such as those conferring antibiotic resistance, but the evolutionary forces shaping their distribution remain unclear. This study challenges the idea that non-conjugative plasmids evolved for high-frequency spread. Using Staphylococcus aureus as a model, we found these plasmids lack key DNA sequences (\"pac\" or \"cos\" sites) essential for efficient phage-mediated transduction, despite such sequences not being costly. While S. aureus plasmids can evolve to enhance phage-mediated mobility by incorporating phage DNA, this strategy proves detrimental. In mixed populations, low plasmid transfer enables plasmids to co-exist and protect host bacteria and neighbors from threats. However, increased movement reduces plasmid diversity, eroding protective benefits and leaving populations vulnerable. Our findings indicate plasmids evolve to restrict movement, maintaining diversity and ensuring survival against threats like antibiotics and phages. This balance explains why plasmid mobility remains low in nature, despite their potential for rapid gene transfer.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 11","pages":"116456"},"PeriodicalIF":6.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
A bacterial exotoxin-triggered plant immune response restricts pathogen growth. 细菌外毒素引发的植物免疫反应限制病原体的生长。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-22 DOI: 10.1016/j.celrep.2025.116457
David Thoms, Melissa Y Chen, Yang Liu, Leah Fulton, Youqing Luo, Daniel E Hiott, Siyu Song, Zayda Morales Moreira, Nicole R Wang, Diego Zorio, Martin Rejzek, Ryan Potter, Philip Carella, Cara H Haney
{"title":"A bacterial exotoxin-triggered plant immune response restricts pathogen growth.","authors":"David Thoms, Melissa Y Chen, Yang Liu, Leah Fulton, Youqing Luo, Daniel E Hiott, Siyu Song, Zayda Morales Moreira, Nicole R Wang, Diego Zorio, Martin Rejzek, Ryan Potter, Philip Carella, Cara H Haney","doi":"10.1016/j.celrep.2025.116457","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116457","url":null,"abstract":"<p><p>For optimal growth and development, hosts must promote healthy symbiotic interactions while restricting pathogens. To ask whether hosts can distinguish phylogenetically similar pathogens and beneficial bacteria, we used two closely related plant root-associated strains within the Pseudomonas fluorescens species complex. Despite having similar immunogenic microbe-associated molecular patterns, one strain is beneficial and the other exhibits exotoxin-dependent virulence. We show that the two strains co-exist in vitro, but the beneficial strain outcompetes the pathogen in the rhizosphere. We find that plants respond to the pathogen, but not the beneficial strain, predominantly via an exotoxin-triggered defense response in roots. The purified exotoxin is sufficient to induce immunity and restrict bacterial growth in a BAK1/BKK1/CERK1-dependent manner. We show that these immune components are also required for balancing the growth between the beneficial and pathogenic strains. We conclude that plant immunity can distinguish phylogenetically similar microbes with distinct lifestyles, in part, through perception of exotoxins.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 11","pages":"116457"},"PeriodicalIF":6.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Distinct immunity protein families mediate compartment-specific neutralization of a bacterial toxin. 不同的免疫蛋白家族介导细菌毒素的室特异性中和。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-22 DOI: 10.1016/j.celrep.2025.116459
Felicity Alcock, Yaping Yang, Justin Deme, Guillermina Casabona, Chriselle Mendonca, Fatima Ulhuq, Susan Lea, Tracy Palmer
{"title":"Distinct immunity protein families mediate compartment-specific neutralization of a bacterial toxin.","authors":"Felicity Alcock, Yaping Yang, Justin Deme, Guillermina Casabona, Chriselle Mendonca, Fatima Ulhuq, Susan Lea, Tracy Palmer","doi":"10.1016/j.celrep.2025.116459","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116459","url":null,"abstract":"<p><p>Staphylococcus aureus utilizes a type VII secretion system (T7SS) to secrete antibacterial toxins targeting competitor bacteria. EsxX is a T7SS substrate protein harboring an N-terminal LXG domain, which is secreted by ST398 strains. We demonstrate that the EsxX C terminus is a membrane-depolarizing toxin with a glycine zipper motif. EsxX is profoundly toxic to bacteria, displaying toxicity from both cytoplasmic and extracellular compartments. A pair of polytopic membrane proteins, ExiCD, protects cells from intoxication by extracellular EsxX. By contrast, a distinct soluble heterodimer, ExiAB, neutralizes cytoplasmic EsxX by sequestration of its glycine zipper motif in a binding groove on ExiB. exiA-exiB co-occur with esxX, consistent with protection from self-toxicity prior to EsxX secretion. By contrast, ExiCD is encoded by both EsxX producers and in antitoxin islands of competitor strains that do not encode EsxX, consistent with providing immunity against the secreted form of the toxin.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 11","pages":"116459"},"PeriodicalIF":6.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma. 靶向肝脏生物钟与酪氨酸激酶抑制可逆转晚期肝细胞癌。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-20 DOI: 10.1016/j.celrep.2025.116313
Baharan Fekry, Savera Aggarwal, Rachel Van Drunen, Rafael Bravo, Andy Escalante, Constance Atkins, Sheng Pan, Zheng Chen, Kai Sun, David R Hall, Mamoun Younes, Kristin Eckel-Mahan
{"title":"Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma.","authors":"Baharan Fekry, Savera Aggarwal, Rachel Van Drunen, Rafael Bravo, Andy Escalante, Constance Atkins, Sheng Pan, Zheng Chen, Kai Sun, David R Hall, Mamoun Younes, Kristin Eckel-Mahan","doi":"10.1016/j.celrep.2025.116313","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116313","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Most patients present at advanced stages, and the effectiveness of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors is constrained by limited patient response. A subset of HCC shows elevated expression of the promoter 2 (\"P2\")-driven hepatocyte nuclear factor 4 alpha (HNF4α) isoform, which directly transcriptionally represses the circadian brain and muscle ARNT-like protein 1 (BMAL1) transcription factor. This subtype of HCC is robustly inhibited by the plant-based flavonoid nobiletin (NOB), a circadian-fortifying compound. Using patient-matched human HCC and serum, we show that BMAL1-deficient HCC shows exaggerated carnitine palmitoyl transferase expression and related metabolite abundance and that P2-HNF4α regulates the carnitine palmitoyl transferase I gene. Finally, using different preclinical models, we show that the anti-tumor activity of TKIs, when they are co-administered with NOB, is maximal. Our results suggest that chronotherapy and combination therapy might provide improved clinical outcomes for individuals with BMAL1-deficient HCC.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 11","pages":"116313"},"PeriodicalIF":6.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Identification of human gut bacteria that produce bioactive serotonin and promote colonic innervation. 产生生物活性血清素并促进结肠神经支配的人类肠道细菌的鉴定。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-20 DOI: 10.1016/j.celrep.2025.116434
Chiara H Moretti, Estelle Grasset, Jiaying Zhu, Gaohua Yang, Louise E Olofsson, Muhammad Tanweer Khan, Per-Olof Bergh, Jee-Hwan Oh, Annika Lundqvist, Tom van Gils, Manuela Krämer, Lisa M Olsson, Piyush Patel, Matthias Mitteregger, Daysi Espinola Monges, Chinmay Dwibedi, Kimberly A Krautkramer, Nienke Koopman, Marcus Henricsson, Andrew J Macpherson, Thue Schwartz, Gianfranco Grompone, Jan-Peter van Pijkeren, Valentina Tremaroli, Stefan Roos, Magnus Simrén, Fredrik Bäckhed
{"title":"Identification of human gut bacteria that produce bioactive serotonin and promote colonic innervation.","authors":"Chiara H Moretti, Estelle Grasset, Jiaying Zhu, Gaohua Yang, Louise E Olofsson, Muhammad Tanweer Khan, Per-Olof Bergh, Jee-Hwan Oh, Annika Lundqvist, Tom van Gils, Manuela Krämer, Lisa M Olsson, Piyush Patel, Matthias Mitteregger, Daysi Espinola Monges, Chinmay Dwibedi, Kimberly A Krautkramer, Nienke Koopman, Marcus Henricsson, Andrew J Macpherson, Thue Schwartz, Gianfranco Grompone, Jan-Peter van Pijkeren, Valentina Tremaroli, Stefan Roos, Magnus Simrén, Fredrik Bäckhed","doi":"10.1016/j.celrep.2025.116434","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116434","url":null,"abstract":"<p><p>The gut microbiota regulates host intestinal serotonin synthesis, thereby promoting the development and maintenance of the enteric nervous system, which controls bowel motility. Functional bowel disorders, including irritable bowel syndrome, are associated with altered serotonin levels and gut microbiota composition. However, it is unclear if the gut microbiota can synthesize bioactive serotonin, which may affect enteric nervous system development. Here, we identify a consortium of the human gut bacteria Limosilactobacillus mucosae and Ligilactobacillus ruminis that synthesizes serotonin in vitro by decarboxylation of 5-hydroxytryptophan and elevates fecal serotonin levels, colonic neuronal density, and serotonin-immunoreactive neurons when introduced into germ-free, serotonin-deficient mice. The consortium normalizes intestinal transit time in germ-free wild-type mice, and we observe decreased fecal abundance of L. mucosae in individuals with irritable bowel syndrome. These findings suggest that specific members of the human gut microbiota synthesize bioactive serotonin that can contribute to gut health.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"116434"},"PeriodicalIF":6.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity. 人类叉头转录因子的错义变异揭示了叉头DNA双特异性的决定因素。
IF 6.9 1区 生物学
Cell reports Pub Date : 2025-10-20 DOI: 10.1016/j.celrep.2025.116427
Jessica King, Stephen S Gisselbrecht, Julie-Alexia Dias, Raehoon Jeong, Elisabeth Rothman, Martha L Bulyk
{"title":"Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.","authors":"Jessica King, Stephen S Gisselbrecht, Julie-Alexia Dias, Raehoon Jeong, Elisabeth Rothman, Martha L Bulyk","doi":"10.1016/j.celrep.2025.116427","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116427","url":null,"abstract":"<p><p>Recognition of specific DNA sequences by transcription factors (TFs) is a key step in transcriptional control of gene expression. While most forkhead (FH) TFs bind either an FKH (RYAAAYA) or an FHL (GACGC) recognition motif, some FHs can bind both motifs. Mechanisms that control whether an FH is monospecific vs. bispecific have remained unknown. Screening a library of 12 reference FH proteins, 61 naturally occurring missense variants including clinical variants, and 22 designed mutant FHs for DNA-binding activity using universal (\"all 10-mer\") protein-binding microarrays revealed non-DNA-contacting residues that control mono- vs. bispecificity. Variation in non-DNA-contacting amino acid residues of TFs is associated with human traits and may play a role in the evolution of TF DNA-binding activities and gene regulatory networks.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 11","pages":"116427"},"PeriodicalIF":6.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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