EMBO Journal最新文献_第2页

Meru co-ordinates spindle orientation with cell polarity and cell cycle progression. Meru协调纺锤体方向与细胞极性和细胞周期进程。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-01 DOI: 10.1038/s44318-025-00420-5

Melissa M McLellan, Birgit L Aerne, Jennifer J Banerjee Dhoul, Maxine V Holder, Tania Auchynnikava, Nicolas Tapon

{"title":"Meru co-ordinates spindle orientation with cell polarity and cell cycle progression.","authors":"Melissa M McLellan, Birgit L Aerne, Jennifer J Banerjee Dhoul, Maxine V Holder, Tania Auchynnikava, Nicolas Tapon","doi":"10.1038/s44318-025-00420-5","DOIUrl":"10.1038/s44318-025-00420-5","url":null,"abstract":"Correct mitotic spindle alignment is essential for tissue architecture and plays an important role in cell fate specification through asymmetric cell division. Spindle tethering factors such as Drosophila Mud (NuMA in mammals) are recruited to the cell cortex and capture astral microtubules, pulling the spindle in the correct orientation. However, how spindle tethering complexes read the cell polarity axis and how spindle attachment is coupled to mitotic progression remains poorly understood. We explore these questions in Drosophila sensory organ precursors (SOPs), which divide asymmetrically to give rise to epidermal mechanosensory bristles. We show that the scaffold protein Meru, which is enriched at the posterior cortex by the Frizzled/Dishevelled planar cell polarity complex, in turn recruits Mud, linking the spindle tethering and polarity machineries. Furthermore, Cyclin A/Cdk1 associates with Meru at the posterior cortex, promoting the formation of the Mud/Meru/Dsh complex via Meru and Dsh phosphorylation. Thus, Meru couples spindle orientation with cell polarity and provides a cell cycle-dependent cue for spindle tethering.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2949-2975"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Nuclear envelope-associated lipid droplets are enriched in cholesteryl esters and increase during inflammatory signaling. 核包膜相关的脂滴富含胆固醇酯，并在炎症信号传导过程中增加。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s44318-025-00423-2

Ábel Szkalisity, Lauri Vanharanta, Hodaka Saito, Csaba Vörös, Shiqian Li, Antti Isomäki, Teemu Tomberg, Clare Strachan, Ilya Belevich, Eija Jokitalo, Elina Ikonen

{"title":"Nuclear envelope-associated lipid droplets are enriched in cholesteryl esters and increase during inflammatory signaling.","authors":"Ábel Szkalisity, Lauri Vanharanta, Hodaka Saito, Csaba Vörös, Shiqian Li, Antti Isomäki, Teemu Tomberg, Clare Strachan, Ilya Belevich, Eija Jokitalo, Elina Ikonen","doi":"10.1038/s44318-025-00423-2","DOIUrl":"10.1038/s44318-025-00423-2","url":null,"abstract":"Cholesteryl esters (CEs) and triacylglycerols (TAGs) are stored in lipid droplets (LDs), but their compartmentalisation is not well understood. Here, we established a hyperspectral stimulated Raman scattering microscopy system to identify and quantitatively assess CEs and TAGs in individual LDs of human cells. We found that nuclear envelope-associated lipid droplets (NE-LDs) were enriched in cholesteryl esters compared to lipid droplets in the cytoplasm. Correlative light-volume-electron microscopy revealed that NE-LDs projected towards the cytoplasm and associated with type II nuclear envelope (NE) invaginations. The nuclear envelope localization of sterol O-acyltransferase 1 (SOAT1) contributed to NE-LD generation, as trapping of SOAT1 to the NE further increased their number. Upon stimulation by the pro-inflammatory cytokine TNFα, the number of NE-LDs moderately increased. Moreover, TNFα-induced NF-κB nuclear translocation was fine-tuned by SOAT1: increased SOAT1 activity and NE-LDs associated with faster NF-κB translocation, whereas reduced SOAT1 activity and NE-LDs associated with slower NF-κB translocation. Our findings suggest that the NE is enriched in CEs and that cholesterol esterification can modulate nuclear translocation.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2774-2802"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system. 干扰素诱导的parp14介导的p62体adp核糖基化需要泛素-蛋白酶体系统。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s44318-025-00421-4

Rameez Raja, Banhi Biswas, Rachy Abraham, Yiran Wang, Che-Yuan Chang, Ivo A Hendriks, Sara C Buch-Larsen, Hongrui Liu, Xingyi Yang, Chenyao Wang, Hien Vu, Anne Hamacher-Brady, Danfeng Cai, Anthony K L Leung

{"title":"Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system.","authors":"Rameez Raja, Banhi Biswas, Rachy Abraham, Yiran Wang, Che-Yuan Chang, Ivo A Hendriks, Sara C Buch-Larsen, Hongrui Liu, Xingyi Yang, Chenyao Wang, Hien Vu, Anne Hamacher-Brady, Danfeng Cai, Anthony K L Leung","doi":"10.1038/s44318-025-00421-4","DOIUrl":"10.1038/s44318-025-00421-4","url":null,"abstract":"Biomolecular condensates are cellular compartments without enveloping membranes, enabling them to dynamically adjust their composition in response to environmental changes through post-translational modifications. Recent work has revealed that interferon-induced ADP-ribosylation (ADPr), which can be reversed by a SARS-CoV-2-encoded hydrolase, is enriched within a condensate. However, the identity of the condensate and the responsible host ADP-ribosyltransferase remain elusive. Here, we demonstrate that interferon induces ADPr through transcriptional activation of PARP14, requiring both the physical presence and catalytic activity of PARP14 for condensate formation. Interferon-induced ADPr colocalizes with PARP14 and its associated E3 ligase, DTX3L. These PARP14/ADPr condensates contain key components of p62 bodies-including the selective autophagy receptor p62, its binding partner NBR1 and the associated protein TAX1BP1, along with K48-linked and K63-linked polyubiquitin chains-but lack the autophagosome marker LC3B. Knockdown of p62 disrupts the formation of these ADPr condensates. Importantly, these structures are unaffected by autophagy inhibition, but depend on ubiquitination and proteasome activity. Taken together, these findings demonstrate that interferon triggers PARP14-mediated ADP-ribosylation in p62 bodies, which requires an active ubiquitin-proteasome system.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2741-2773"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

A bacterial network of T3SS effectors counteracts host pro-inflammatory responses and cell death to promote infection. 由 T3SS 效应器组成的细菌网络可抵消宿主的促炎反应和细胞死亡，从而促进感染。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1038/s44318-025-00412-5

Hui Wen Yeap, Ghin Ray Goh, Safwah Nasuha Rosli, Hai Shin Pung, Cristina Giogha, Vik Ven Eng, Jaclyn S Pearson, Elizabeth L Hartland, Kaiwen W Chen

{"title":"A bacterial network of T3SS effectors counteracts host pro-inflammatory responses and cell death to promote infection.","authors":"Hui Wen Yeap, Ghin Ray Goh, Safwah Nasuha Rosli, Hai Shin Pung, Cristina Giogha, Vik Ven Eng, Jaclyn S Pearson, Elizabeth L Hartland, Kaiwen W Chen","doi":"10.1038/s44318-025-00412-5","DOIUrl":"10.1038/s44318-025-00412-5","url":null,"abstract":"Innate immune signalling and cell death pathways are highly interconnected processes involving receptor-interacting protein kinases (RIPKs) as mediators of potent anti-microbial responses. However, these processes are often antagonised by bacterial type III secretion system (T3SS) effectors, and the cellular mechanisms by which the host retaliates are not completely understood. Here, we demonstrate that during Citrobacter rodentium infection, murine macrophages and colonic epithelial cells exhibit RIPK1 kinase-dependent caspase-8 activation to counteract NleE effector-mediated suppression of pro-inflammatory signalling. While C. rodentium injects into the host cells a second effector, NleB, to block caspase-8 signalling, macrophages respond by triggering RIPK3-mediated necroptosis, whereupon a third T3SS effector, EspL, acts to inactivate necroptosis. We further show that NleB and EspL collaborate to suppress caspase-8 and NLRP3 inflammasome activation in macrophages. Our findings suggest that C. rodentium has evolved to express a complex network of effectors as an adaptation to the importance of cell death for anti-bacterial defence in the host-pathogen arms race.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2424-2445"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

S-palmitoylation modulates ATG2-dependent non-vesicular lipid transport during starvation-induced autophagy. 在饥饿诱导的自噬过程中，S-棕榈酰化可调节 ATG2 依赖性非囊泡脂质转运。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1038/s44318-025-00410-7

Wenhui Zheng, Maomao Pu, Sai Zeng, Hongtao Zhang, Qian Wang, Tao Chen, Tianhua Zhou, Chunmei Chang, Dante Neculai, Wei Liu

{"title":"S-palmitoylation modulates ATG2-dependent non-vesicular lipid transport during starvation-induced autophagy.","authors":"Wenhui Zheng, Maomao Pu, Sai Zeng, Hongtao Zhang, Qian Wang, Tao Chen, Tianhua Zhou, Chunmei Chang, Dante Neculai, Wei Liu","doi":"10.1038/s44318-025-00410-7","DOIUrl":"10.1038/s44318-025-00410-7","url":null,"abstract":"Lipid transfer proteins mediate the non-vesicular transport of lipids at membrane contact sites to regulate the lipid composition of organelle membranes. Despite significant recent advances in our understanding of the structural basis for lipid transfer, its functional regulation remains unclear. In this study, we report that S-palmitoylation modulates the cellular function of ATG2, a rod-like lipid transfer protein responsible for transporting phospholipids from the endoplasmic reticulum (ER) to phagophores during autophagosome formation. During starvation-induced autophagy, ATG2A undergoes depalmitoylation as the balance between ZDHHC11-mediated palmitoylation and APT1-mediated depalmitoylation. Inhibition of ATG2A depalmitoylation leads to impaired autophagosome formation and disrupted autophagic flux. Further, in cell and in vitro analyses demonstrate that S-palmitoylation at the C-terminus of ATG2A anchors the C-terminus to the ER. Depalmitoylation detaches the C-terminus from the ER membrane, enabling it to interact with phagophores and promoting their growth. These findings elucidate a S-palmitoylation-dependent regulatory mechanism of cellular ATG2, which may represent a broad regulatory strategy for lipid transport mediated by bridge-like transporters within cells.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2596-2619"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Author Correction: A human progeria-associated BAF-1 mutation modulates gene expression and accelerates aging in C. elegans. 作者更正：人类早衰相关的BAF-1突变调节秀丽隐杆线虫的基因表达并加速衰老。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 DOI: 10.1038/s44318-025-00432-1

Raquel Romero-Bueno, Adrián Fragoso-Luna, Cristina Ayuso, Nina Mellmann, Alan Kavsek, Christian G Riedel, Jordan D Ward, Peter Askjaer

引用次数: 0

Mitochondrial fatty acid oxidation regulates adult muscle stem cell function through modulating metabolic flux and protein acetylation. 线粒体脂肪酸氧化通过调节代谢通量和蛋白质乙酰化调节成体肌肉干细胞的功能。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-10 DOI: 10.1038/s44318-025-00397-1

Feng Yue, Lijie Gu, Jiamin Qiu, Stephanie N Oprescu, Linda M Beckett, Jessica M Ellis, Shawn S Donkin, Shihuan Kuang

{"title":"Mitochondrial fatty acid oxidation regulates adult muscle stem cell function through modulating metabolic flux and protein acetylation.","authors":"Feng Yue, Lijie Gu, Jiamin Qiu, Stephanie N Oprescu, Linda M Beckett, Jessica M Ellis, Shawn S Donkin, Shihuan Kuang","doi":"10.1038/s44318-025-00397-1","DOIUrl":"10.1038/s44318-025-00397-1","url":null,"abstract":"During homeostasis and regeneration, satellite cells, the resident stem cells of skeletal muscle, have distinct metabolic requirements for fate transitions between quiescence, proliferation and differentiation. However, the contribution of distinct energy sources to satellite cell metabolism and function remains largely unexplored. Here, we uncover a role of mitochondrial fatty acid oxidation (FAO) in satellite cell integrity and function. Single-cell RNA sequencing revealed progressive enrichment of mitochondrial FAO and downstream pathways during activation, proliferation and myogenic commitment of satellite cells. Deletion of Carnitine palmitoyltransferase 2 (Cpt2), the rate-limiting enzyme in FAO, hampered muscle stem cell expansion and differentiation upon acute muscle injury, markedly delaying regeneration. Cpt2 deficiency reduces acetyl-CoA levels in satellite cells, impeding the metabolic flux and acetylation of selective proteins including Pax7, the central transcriptional regulator of satellite cells. Notably, acetate supplementation restored cellular metabolic flux and partially rescued the regenerative defects of Cpt2-null satellite cells. These findings highlight an essential role of fatty acid oxidation in controlling satellite cell function and suggest an integration of lipid metabolism and protein acetylation in adult stem cells.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2566-2595"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Dimerization of GAS2 mediates crosslinking of microtubules and F-actin. GAS2的二聚化介导微管和f -肌动蛋白的交联。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-01 DOI: 10.1038/s44318-025-00415-2

Jiancheng An, Tsuyoshi Imasaki, Akihiro Narita, Shinsuke Niwa, Ryohei Sasaki, Tsukasa Makino, Ryo Nitta, Masahide Kikkawa

{"title":"Dimerization of GAS2 mediates crosslinking of microtubules and F-actin.","authors":"Jiancheng An, Tsuyoshi Imasaki, Akihiro Narita, Shinsuke Niwa, Ryohei Sasaki, Tsukasa Makino, Ryo Nitta, Masahide Kikkawa","doi":"10.1038/s44318-025-00415-2","DOIUrl":"10.1038/s44318-025-00415-2","url":null,"abstract":"The spectraplakin family protein GAS2 was originally identified as a growth arrest-specific protein, and recent studies have revealed its involvement in multiple cellular processes. Its dual interaction with actin filaments and microtubules highlights its essential role in cytoskeletal organization, such as cell division, apoptosis, and possibly tumorigenesis. However, the structural basis of cytoskeletal dynamics regulation by GAS2 remains unclear. In this study, we present cryo-electron microscopy structures of the GAS2 type 3 calponin homology domain (CH3) in complex with F-actin at 2.8 Å resolution, thus solving the first type CH3 domain structure bound to F-actin and confirming its actin-binding activity. We also provide the first near-atomic resolution cryo-EM structure of the GAS2-GAR domain bound to microtubules and identify conserved microtubule-binding residues. Our biochemical experiments show that GAS2 promotes microtubule nucleation and polymerization, and that its C-terminal region is essential for dimerization, bundling of both F-actin and microtubules, and microtubule nucleation. As mutations leading to expression of C-terminally truncated GAS2 have been linked to hearing loss, these findings suggest that the disruption of GAS2-dependent cytoskeletal organisation could underlie auditory dysfunction.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2997-3024"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

T-cell-derived IFN-γ suppresses T follicular helper cell differentiation and antibody responses. T细胞来源的IFN-γ抑制T滤泡辅助细胞分化和抗体反应。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-01 DOI: 10.1038/s44318-025-00414-3

Eleonora Sala, Maria Nelli, Chiara Laura, Pietro Di Lucia, Cristian Gabriel Beccaria, Elisa B Bono, Marta Mangione, Davide Marotta, Valentina Sperto, Marta Grillo, Leonardo Giustini, Fabio Tosi, Jia Nie, Daehong Kim, Giuliana Furiato, Chiara Malpighi, Eleonora Consolo, Burkhard Becher, Eyal David, Merav Cohen, Amir Giladi, Ido Amit, Remy Bosselut, Luca G Guidotti, Matteo Iannacone, Mirela Kuka

{"title":"T-cell-derived IFN-γ suppresses T follicular helper cell differentiation and antibody responses.","authors":"Eleonora Sala, Maria Nelli, Chiara Laura, Pietro Di Lucia, Cristian Gabriel Beccaria, Elisa B Bono, Marta Mangione, Davide Marotta, Valentina Sperto, Marta Grillo, Leonardo Giustini, Fabio Tosi, Jia Nie, Daehong Kim, Giuliana Furiato, Chiara Malpighi, Eleonora Consolo, Burkhard Becher, Eyal David, Merav Cohen, Amir Giladi, Ido Amit, Remy Bosselut, Luca G Guidotti, Matteo Iannacone, Mirela Kuka","doi":"10.1038/s44318-025-00414-3","DOIUrl":"10.1038/s44318-025-00414-3","url":null,"abstract":"CD4+ T cells play a critical role in antiviral humoral and cellular immune responses. We have previously reported that subcutaneous lymphocytic choriomeningitis virus (s.c. LCMV) infection is characterized by a stark compartmentalization of CD4+ T cells, leading to strong TH1 cell polarization but virtually absent T follicular helper (TFH) cells, key drivers of humoral immunity. Here, we investigate the mechanisms responsible for this impaired TFH differentiation. We show that T-bet+ cells induced by LCMV infection encompass a TH1 cell subset expressing granzyme B (GzmB), and a Tcf-1+ cell subset that retains the potential for TFH differentiation without expressing mature TFH markers. Notably, IFN-γ blockade enables full differentiation of Tcf-1+ cells into TFH cells, formation of germinal centers, and increased antibody production. Suppression of TFH cells by IFN-γ is not directly mediated by CD4+ T cells but rather involves another cell type, likely dendritic cells (DCs). Our study provides novel insights into the mechanisms underlying early CD4+ T-cell polarization and humoral responses to viruses, with the potential to facilitate the development of effective vaccine strategies.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2400-2423"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Nanoscale analysis of human G1 and metaphase chromatin in situ. 人G1和中期染色质的纳米级原位分析。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-17 DOI: 10.1038/s44318-025-00407-2

Jon Ken Chen, Tingsheng Liu, Shujun Cai, Weimei Ruan, Cai Tong Ng, Jian Shi, Uttam Surana, Lu Gan

{"title":"Nanoscale analysis of human G1 and metaphase chromatin in situ.","authors":"Jon Ken Chen, Tingsheng Liu, Shujun Cai, Weimei Ruan, Cai Tong Ng, Jian Shi, Uttam Surana, Lu Gan","doi":"10.1038/s44318-025-00407-2","DOIUrl":"10.1038/s44318-025-00407-2","url":null,"abstract":"The structure of chromatin at the nucleosome level inside cells is still incompletely understood. Here we present in situ electron cryotomography analyses of chromatin in both G1 and metaphase RPE-1 cells. G1 nucleosomes are concentrated in globular chromatin domains, and metaphase nucleosomes are concentrated in the chromatids. Classification analysis reveals that canonical mononucleosomes, and in some conditions ordered stacked dinucleosomes and mononucleosomes with a disordered gyre-proximal density, are abundant in both cell-cycle states. We do not detect class averages that have more than two stacked nucleosomes or side-by-side dinucleosomes, suggesting that groups of more than two nucleosomes are heterogeneous. Large multi-megadalton structures are abundant in G1 nucleoplasm, but not found in G1 chromatin domains and metaphase chromatin. The macromolecular phenotypes studied here represent a starting point for the comparative analysis of compaction in normal vs. unhealthy human cells, in other cell-cycle states, other organisms, and in vitro chromatin assemblies.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2658-2694"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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