The FEBS journal最新文献_第3页

Protein tandem repeats that produce frameshifts can generate new structural states and functions. 产生帧移的蛋白质串联重复序列可以产生新的结构状态和功能。

IF 4.2

The FEBS journal Pub Date : 2025-09-24 DOI: 10.1111/febs.70273

Zarifa Osmanli, Gudrun Aldrian, Jeremy Leclercq, Theo Falgarone, Santiago M Gómez Bergna, Denis N Prada Gori, Andrew V Oleinikov, Ilham Shahmuradov, Andrey V Kajava

{"title":"Protein tandem repeats that produce frameshifts can generate new structural states and functions.","authors":"Zarifa Osmanli, Gudrun Aldrian, Jeremy Leclercq, Theo Falgarone, Santiago M Gómez Bergna, Denis N Prada Gori, Andrew V Oleinikov, Ilham Shahmuradov, Andrey V Kajava","doi":"10.1111/febs.70273","DOIUrl":"https://doi.org/10.1111/febs.70273","url":null,"abstract":"The genetic code uses three-nucleotide units to encode each amino acid in proteins. Insertions or deletions of nucleotides not divisible by three shift the reading frames, resulting in significantly different protein sequences. These events are disruptive but can also create variability important for evolution. Previous studies suggested that the genetic code and gene sequences evolve to minimize frameshift effects, maintaining similar physicochemical properties to their reference proteins. Here, we focused on tandem repeat sequences, known as frameshift hotspots. Using cutting-edge bioinformatics tools, we compared reference and frameshifted protein sequences within tandem repeats across 50 prokaryotic and eukaryotic proteomes. We showed that, in contrast to the general tendency, frameshifts within these regions, especially with short repeats, lead to a significant increase in hydrophobicity and arginine content. Additionally, the frameshifts, particularly in short tandem repeats, rearrange transmembrane regions, potentially converting soluble proteins into membrane proteins and vice versa. Given their occurrence in rapidly evolving, essential proteins, such changes may promote rapid adaptability. Our large-scale alphafold modeling suggested that frameshift events can generate novel structures and functions, enabling the synthesis of multiple protein variants within the same coding region. Overall, frameshifts cause more drastic changes in tandem repeat sequences compared to non-repetitive sequences and therefore can be a primary cause of altered functions, cellular localization, and the development of various pathologies.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and functional dissection of the WH2/DAD motif of INF2, a formin linked to human inherited degenerative disorders. 与人类遗传性退行性疾病相关的双胍蛋白INF2的WH2/DAD基序的结构和功能解剖。

IF 4.2

The FEBS journal Pub Date : 2025-09-24 DOI: 10.1111/febs.70271

Leticia Labat-de-Hoz, Laura Fernández-Martín, Paula Morales, Isabel Correas, María Ángeles Jiménez, Miguel Angel Alonso

{"title":"Structural and functional dissection of the WH2/DAD motif of INF2, a formin linked to human inherited degenerative disorders.","authors":"Leticia Labat-de-Hoz, Laura Fernández-Martín, Paula Morales, Isabel Correas, María Ángeles Jiménez, Miguel Angel Alonso","doi":"10.1111/febs.70271","DOIUrl":"https://doi.org/10.1111/febs.70271","url":null,"abstract":"Inverted formin-2 (INF2), a formin linked to inherited renal and neurological disorders, exhibits pathogenic variants that lead to deregulated actin polymerization and nuclear aberrations, ultimately compromising cell viability. Most formins contain a diaphanous autoregulatory domain (DAD) and a diaphanous inhibitory domain (DID), which interact to keep the molecule in an inactive state. The DAD consists of a short sequence with an N-terminal region rich in hydrophobic residues and a C-terminal segment abundant in basic residues, resembling WASP homology 2 (WH2) actin-binding domains. Based on its sequence and actin-binding ability, the DAD of INF2 qualifies as a WH2 motif. In this study, we investigated the structure of the INF2 WH2/DAD by nuclear magnetic resonance (NMR) and explored its functional role. Our analysis revealed that the WH2/DAD forms a single α-helix in both H2O and 30% 2,2,2-trifluoroethanol that differs from the conformations observed in WH2-actin and DAD-DID crystal structures. Cells expressing INF2 containing only the hydrophobic region of the WH2/DAD exhibited higher F-actin levels and frequencies of nuclear abnormalities, phenocopying the effect of pathogenic INF2 DID variants. In contrast, deletion of the entire WH2/DAD, or of the hydrophobic region alone, abolishes INF2 activity. Neither these deletions nor WH2/DAD variants carrying naturally occurring missense mutations induced any detectable nuclear effects. These findings suggest that the WH2/DAD undergoes a conformational change to facilitate actin binding and that the hydrophobic region is essential for INF2-mediated actin polymerization. INF2 WH2/DAD variants with deleterious cellular effects appear to be rare in, or absent from, the human population.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

D1/D5 receptor activation promotes long-term potentiation and synaptic tagging/capture in hippocampal area CA2. D1/D5受体激活促进海马区CA2的长期增强和突触标记/捕获。

IF 4.2

The FEBS journal Pub Date : 2025-09-22 DOI: 10.1111/febs.70266

Kevin Chua, Yee Song Chong, Sreedharan Sajikumar

{"title":"D1/D5 receptor activation promotes long-term potentiation and synaptic tagging/capture in hippocampal area CA2.","authors":"Kevin Chua, Yee Song Chong, Sreedharan Sajikumar","doi":"10.1111/febs.70266","DOIUrl":"https://doi.org/10.1111/febs.70266","url":null,"abstract":"Hippocampal area CA2 plays an important role in social memory formation. However, CA2 is characterised by plasticity-resistant Schaffer Collateral-CA2 (SC-CA2) synapses and highly plastic entorhinal cortex-CA2 (EC-CA2) synapses. Despite abundant dopaminergic input, the relationship between dopamine signalling and area CA2 synaptic plasticity remains unexplored. Here, we show that SKF-38393-mediated dopamine D1-like receptor (dopamine D1 and D5 receptors (D1R and D5R)) activation differentially primes CA2 inputs in an N-methyl-D-aspartate receptor (NMDAR)- and protein synthesis-dependent manner. We defined an inverted U-shape relationship between SKF-38393 concentration and EC-CA2 potentiation. Additionally, we observed a priming effect on SC-CA2 plasticity with 50 μm SKF-38393, relieving plasticity resistance. We also demonstrated that this effect follows canonical protein kinase A (PKA) signalling. Collectively, our results show that D1R activation primes the CA2 for synaptic plasticity. Thus, we propose a link between neuropsychiatric diseases related to impaired dopamine transmission and deficits in hippocampus-dependent social memory.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The SARS-CoV-2 spike protein interacts with HAX1 to modulate cellular stress responses through activation of the UPR. SARS-CoV-2刺突蛋白与HAX1相互作用，通过激活UPR调节细胞应激反应。

IF 4.2

The FEBS journal Pub Date : 2025-09-21 DOI: 10.1111/febs.70259

Tony Avril, Elodie Lafont

{"title":"The SARS-CoV-2 spike protein interacts with HAX1 to modulate cellular stress responses through activation of the UPR.","authors":"Tony Avril, Elodie Lafont","doi":"10.1111/febs.70259","DOIUrl":"https://doi.org/10.1111/febs.70259","url":null,"abstract":"During cell infection, viruses maintain the lifespan of host cells by preserving key functions of cellular organelles such as the endoplasmic reticulum (ER) and mitochondria to guarantee protein secretion and energy production. The host secretory pathway is rapidly hijacked to produce viral proteins and reconstitute viral particles for further viral dissemination. However, secreted protein synthesis and proper folding are tightly regulated in the host ER to maintain homeostasis, otherwise this organelle is subjected to ER stress that triggers an adaptive response named the unfolded protein response (UPR). The UPR first aims at restoring ER function by producing enzymes to correct or eliminate misfolded proteins. If ER stress remains unresolved, the UPR triggers cell death. In the work published by Zhu et al. in this issue of The FEBS Journal, the authors explore a previously undescribed molecular hijacking function of SARS-CoV-2 to limit host cell death. Indeed, the viral spike protein directly interacts with the host HAX1 molecule to promote UPR activation, limiting the production of deleterious reactive oxygen species and mitochondrial dysfunction to maintain host cell survival.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aquaporin-1, aquaporin-3 and aquaporin-5 differentially modulate cell biophysical and biomechanical properties, impacting cell stiffness and cell-cell adhesion. 水通道蛋白-1、水通道蛋白-3和水通道蛋白-5调节细胞的生物物理和生物力学特性，影响细胞刚度和细胞间粘附。

IF 4.2

The FEBS journal Pub Date : 2025-09-21 DOI: 10.1111/febs.70269

Catarina Pimpão, Filomena Almeida Carvalho, Inês Vieira da Silva, Andreia Barateiro, Nuno Correia Santos, Graça Soveral

{"title":"Aquaporin-1, aquaporin-3 and aquaporin-5 differentially modulate cell biophysical and biomechanical properties, impacting cell stiffness and cell-cell adhesion.","authors":"Catarina Pimpão, Filomena Almeida Carvalho, Inês Vieira da Silva, Andreia Barateiro, Nuno Correia Santos, Graça Soveral","doi":"10.1111/febs.70269","DOIUrl":"https://doi.org/10.1111/febs.70269","url":null,"abstract":"Aquaporins (AQPs) are transmembrane proteins that facilitate the movement of water, glycerol, and other small solutes across cell membranes. AQP1, AQP3, and AQP5 are overexpressed in cancer, contributing to cancer cell proliferation, migration, angiogenesis, and metastasis. Previously, we showed that silencing AQP3 and/or AQP5 in human pancreatic ductal adenocarcinoma cells induced morphological changes and decreased cell-cell adhesion, with AQP5 modulating cell stiffness and membrane fluidity, suggesting that AQPs can impact tumor progression via modulation of cell biophysical and biomechanical properties. In this study, we overexpressed AQP1, AQP3, or AQP5 individually in human kidney (HEK-293 T) cells to investigate their individual effects on biological processes, cell morphology, and biomechanical features. After validating AQP expression and function, we evaluated their impact on cell proliferation and migration. Although cell proliferation remained unaffected, AQP5 overexpression enhanced cell migration. Afterwards, we assessed the effect of these AQPs on cell morphological properties through atomic force microscopy (AFM) imaging. AQP1-, AQP3-, and AQP5-overexpressing cells showed no significant changes in cell morphology. AFM-based force spectroscopy demonstrated that AQP1 overexpression increased both cell stiffness and cell-cell adhesion, AQP3 overexpression enhanced cell stiffness but slightly reduced cell-cell adhesion, whereas AQP5 overexpression increased both cell elasticity and cell-cell adhesion. Thus, AQP1, AQP3, and AQP5 may play a crucial role in promoting tumor growth and invasion by differentially modulating cell stiffness and cell-cell adhesion.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vaspin identified as a DNA-binding serpin with functional consequences for protease inhibition. Vaspin是一种dna结合丝氨酸蛋白，具有抑制蛋白酶的功能。

IF 4.2

The FEBS journal Pub Date : 2025-09-21 DOI: 10.1111/febs.70270

Kevin Möhlis, Abibe Useini, Heike Betat, Sonja Bonin, Helen Broghammer, Rima Nuwayhid, Stefan Langer, Mario Mörl, Norbert Sträter, John T Heiker

{"title":"Vaspin identified as a DNA-binding serpin with functional consequences for protease inhibition.","authors":"Kevin Möhlis, Abibe Useini, Heike Betat, Sonja Bonin, Helen Broghammer, Rima Nuwayhid, Stefan Langer, Mario Mörl, Norbert Sträter, John T Heiker","doi":"10.1111/febs.70270","DOIUrl":"https://doi.org/10.1111/febs.70270","url":null,"abstract":"Vaspin is highly expressed not only in the skin but also in the liver and adipose tissue. It counteracts inflammation and oxidative stress in inflammatory skin diseases, obesity, and associated metabolic disorders, in part by inhibiting the kallikrein proteases KLK7 and KLK14. Vaspin binds the cell-surface low-density lipoprotein receptor-related protein 1 (LRP1) with nanomolar affinity, and is rapidly internalized into adipocytes and other cells. We found intracellular vaspin partially localized in the nucleus. Since vaspin binds heparin and inorganic polyphosphates, we investigated the DNA binding of vaspin. Using DNA-affinity chromatography and differential radial capillary action of ligand assays, we found high-affinity binding to random sequences of single- and double-stranded DNA for both vaspin and KLK7. Furthermore, KLK7 inhibition was accelerated fivefold in the presence of DNA molecules at least 40 bases in length. We previously identified the heparin-binding site at a basic patch on the central beta-sheet A of vaspin. In the current work, we determined the crystal structure of polyphosphate P45-bound vaspin, which confirmed previously identified residues mutated to generate a nonheparin-binding (NHB) vaspin variant. While NHB vaspin failed to bind heparin and polyP45, it still bound DNA with high affinity and accelerated protease inhibition. Mutation of closely spaced basic residues in helix A and helix G did not significantly alter DNA binding. In conclusion, we have identified vaspin as the second human DNA-binding serpin. While the exact mode of the nonspecific interaction remains unclear, it accelerates protease inhibition and likely contributes to the nuclear localization observed for internalized vaspin and may allow for intracellular effects.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung organoids as a human system for Mycobacteria infection modeling and drug testing. 肺类器官作为分枝杆菌感染的人体系统建模和药物测试。

IF 4.2

The FEBS journal Pub Date : 2025-09-21 DOI: 10.1111/febs.70265

Stephen Adonai Leon-Icaza, Romain Vergé, Raoul Mazars, Laurence Berry, Céline Cougoule

{"title":"Lung organoids as a human system for Mycobacteria infection modeling and drug testing.","authors":"Stephen Adonai Leon-Icaza, Romain Vergé, Raoul Mazars, Laurence Berry, Céline Cougoule","doi":"10.1111/febs.70265","DOIUrl":"https://doi.org/10.1111/febs.70265","url":null,"abstract":"Mycobacterial infections remain a global public health challenge. Each year, high rates of morbidity and mortality worldwide are a consequence of chronic respiratory infections due to Mycobacteria. According to the World Health Organization (WHO), in 2023, 10.8 million individuals fell ill with Mycobacterium tuberculosis (Mtb), resulting in an estimated 1.25 million deaths. This positions tuberculosis (TB) as the leading cause of death from a single pathogen worldwide after the coronavirus disease (COVID-19) pandemic. On the other hand, the cases of people affected by nontuberculous mycobacteria (NTM) have risen globally, but the precise incidence and prevalence of both pulmonary and extrapulmonary disease remain unknown. In Europe, nontuberculous mycobacterial pulmonary diseases affect between 0.2 and 2.9 per 100 000 individuals, mainly patients with cystic fibrosis (CF) and non-CF bronchiectasis. The diagnosis and treatment of mycobacterial infections are challenging and complex, frequently requiring long-duration treatments with several antibiotics, which in most cases leads to poor patient outcomes. As the role of immune cells has been extensively assessed, in this Review, we summarize the current knowledge about the contribution of epithelial cells in the early steps of Mycobacteria infections. Additionally, we describe how human lung organoid technology provides new tools to better understand host-Mycobacteria interactions in the airways and test new therapeutic targets.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atg18 facilitates autophagosome formation via its Atg8-interacting motif in Saccharomyces cerevisiae. 在酿酒酵母中，Atg18通过与atg8相互作用的基序促进自噬体的形成。

IF 4.2

The FEBS journal Pub Date : 2025-09-16 DOI: 10.1111/febs.70257

Tianzhi Li, Xiazhen Li, Miaomiao Li, Tao Yuan, Cong Ma

{"title":"Atg18 facilitates autophagosome formation via its Atg8-interacting motif in Saccharomyces cerevisiae.","authors":"Tianzhi Li, Xiazhen Li, Miaomiao Li, Tao Yuan, Cong Ma","doi":"10.1111/febs.70257","DOIUrl":"https://doi.org/10.1111/febs.70257","url":null,"abstract":"Autophagy, an essential process in eukaryotic cells, entails the sequestration and degradation of cytosolic components and organelles following fusion with the lysosome or vacuole. Autophagy-related protein 18 (Atg18), a key autophagy-related protein, binds phosphatidylinositol-3-phosphate (PI3P) to localize to autophagosomal membranes, where it recruits Atg2 to mediate lipid transfer during autophagosome biogenesis. Although the roles of Atg18 in autophagy are well established, whether this protein exerts additional regulatory functions in this process remains to be elucidated. Here, we report the weak interactions between Atg18 and Atg8 or Atg16 mediated by the Atg8-interacting motif (AIM) within Atg18. Disruption of the AIM in Atg18 leads to reduced autophagosome formation and diminished autophagic activity. Moreover, we demonstrate that Atg18 is involved in the recruitment of Atg8 to the autophagosome and facilitates the C-terminal cleavage of Atg8 by Atg4. Furthermore, the Atg18-Atg8 complex can be dissociated by Atg3, enabling free Atg18 to subsequently recruit Atg16 to the autophagosome, preparing for Atg8 lipidation. Thus, our findings unveil previously unknown roles for Atg18 in downstream factor recruitment and Atg4 cleavage during autophagosome formation via its AIM.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Highly divergent apicomplexan cytoskeletons provide additional models for actin biology. 高度分化的顶复合体细胞骨架为肌动蛋白生物学提供了额外的模型。

IF 4.2

The FEBS journal Pub Date : 2025-09-13 DOI: 10.1111/febs.70263

Yukino Kobayashi, Ross G Douglas

引用次数: 0

SET domain containing 3 (SETD3) interacts with bromodomain-containing protein 2 (BRD2) and coordinates its chromatin association in mouse embryonic stem cells. 在小鼠胚胎干细胞中，SET结构域3 （SETD3）与含溴结构域蛋白2 （BRD2）相互作用并协调其染色质关联。

IF 4.2

The FEBS journal Pub Date : 2025-09-13 DOI: 10.1111/febs.70261

Dersu Sezginmert, Gozde Guven, Ceren Alganatay, Deniz Ak, Nihal Terzi Cizmecioglu

{"title":"SET domain containing 3 (SETD3) interacts with bromodomain-containing protein 2 (BRD2) and coordinates its chromatin association in mouse embryonic stem cells.","authors":"Dersu Sezginmert, Gozde Guven, Ceren Alganatay, Deniz Ak, Nihal Terzi Cizmecioglu","doi":"10.1111/febs.70261","DOIUrl":"https://doi.org/10.1111/febs.70261","url":null,"abstract":"Regulation of cell fate decisions during early embryonic development requires precise temporal and spatial control. The embryonic stem cell (ESC) transcription factor network maintains a delicate balance between self-renewal and differentiation by suppressing lineage-specific transcription while upregulating pluripotency factors. Our previous studies highlighted a critical role for the SET domain-containing protein actin-histidine N-methyltransferase (SETD3) in endoderm differentiation of mouse embryonic stem cells (mESCs). However, its specific functions within the nuclear context remained poorly understood. In this study, we used mass spectrometry to identify nuclear protein partners of SETD3. Our findings revealed that SETD3 interacts with the transcription factor CP2-like protein 1 (TFCP2L1; a pluripotency transcription factor) and bromodomain-containing protein 2 (BRD2) in the nucleus. Notably, our study highlights an essential role of SETD3 in the recruitment of BRD2 to chromatin in mESCs. Through domain deletions and proximity ligation assays, we established that this interaction is dependent on the RSB domain of SETD3 and potentially the BD2 domain of BRD2. The absence of SETD3 led to considerable alterations in the chromatin environment and a significant reduction in BRD2 recruitment, resulting in transcriptional changes. Our findings highlight the significant role of SETD3-dependent BRD2 recruitment in regulating chromatin dynamics and transcriptional outcomes in mESCs, enhancing our understanding of its role in ESC pluripotency exit and lineage commitment.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0