EMBO Reports最新文献

KMT5C leverages disorder to optimize cooperation with HP1 for heterochromatin retention. KMT5C 利用紊乱来优化与 HP1 的合作，以保持异染色质。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-19 DOI: 10.1038/s44319-024-00320-5

Justin W Knechtel, Hilmar Strickfaden, Kristal Missiaen, Joanne D Hadfield, Michael J Hendzel, D Alan Underhill

{"title":"KMT5C leverages disorder to optimize cooperation with HP1 for heterochromatin retention.","authors":"Justin W Knechtel, Hilmar Strickfaden, Kristal Missiaen, Joanne D Hadfield, Michael J Hendzel, D Alan Underhill","doi":"10.1038/s44319-024-00320-5","DOIUrl":"https://doi.org/10.1038/s44319-024-00320-5","url":null,"abstract":"A defining feature of constitutive heterochromatin compartments is the heterochromatin protein-1 (HP1) family, whose members display fast internal mobility and rapid exchange with the surrounding nucleoplasm. Here, we describe a paradoxical state for the lysine methyltransferase KMT5C characterized by rapid internal diffusion but minimal nucleoplasmic exchange. This retentive behavior is conferred by sparse sequence features that constitute two modules tethered by an intrinsically disordered linker. While both modules harbor variant HP1 interaction motifs, the first comprises adjacent sequences that increase affinity using avidity. The second motif increases HP1 effective concentration to further enhance affinity in a context-dependent manner, which is evident using distinct heterochromatin recruitment strategies and heterologous linkers with defined conformational ensembles. Despite the linker sequence being highly divergent, it is under evolutionary constraint for functional length, suggesting conformational buffering can support cooperativity between modules across distant orthologs. Overall, we show that KMT5C has evolved a robust tethering strategy that uses minimal sequence determinants to harness highly dynamic HP1 proteins for retention within heterochromatin compartments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675462","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

Regulating translation in aging: from global to gene-specific mechanisms. 衰老过程中的翻译调控：从全球机制到基因特异性机制。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-19 DOI: 10.1038/s44319-024-00315-2

Mathilde Solyga, Amitabha Majumdar, Florence Besse

引用次数: 0

Interplay between the brain and adipose tissue: a metabolic conversation. 大脑与脂肪组织之间的相互作用：新陈代谢的对话。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-18 DOI: 10.1038/s44319-024-00321-4

Francisco Díaz-Castro, Eugenia Morselli, Marc Claret

{"title":"Interplay between the brain and adipose tissue: a metabolic conversation.","authors":"Francisco Díaz-Castro, Eugenia Morselli, Marc Claret","doi":"10.1038/s44319-024-00321-4","DOIUrl":"10.1038/s44319-024-00321-4","url":null,"abstract":"The central nervous system and adipose tissue interact through complex communication. This bidirectional signaling regulates metabolic functions. The hypothalamus, a key homeostatic brain region, integrates exteroceptive and interoceptive signals to control appetite, energy expenditure, glucose, and lipid metabolism. This regulation is partly achieved via the nervous modulation of white (WAT) and brown (BAT) adipose tissue. In this review, we highlight the roles of sympathetic and parasympathetic innervation in regulating WAT and BAT activities, such as lipolysis and thermogenesis. Adipose tissue, in turn, plays a dual role as an energy reservoir and an endocrine organ, secreting hormones that influence brain function and metabolic health. In addition, this review focuses on recently uncovered communication pathways, including extracellular vesicles and neuro-mesenchymal units, which add new layers of regulation and complexity to the brain-adipose tissue interaction. Finally, we also examine the consequences of disrupted communication between the brain and adipose tissue in metabolic disorders like obesity and type-2 diabetes, emphasizing the potential for new therapeutic strategies targeting these pathways to improve metabolic health.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667116","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

Novel integrated multiomics analysis reveals a key role for integrin beta-like 1 in wound scarring. 新颖的多组学综合分析揭示了整合素 beta 样 1 在伤口瘢痕形成中的关键作用。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-18 DOI: 10.1038/s44319-024-00322-3

Sang-Eun Kim, Ryota Noda, Yu-Chen Liu, Yukari Nakajima, Shoichiro Kameoka, Daisuke Motooka, Seiya Mizuno, Satoru Takahashi, Kento Takaya, Takehiko Murase, Kazuya Ikematsu, Katsiaryna Tratsiakova, Takahiro Motoyama, Masahiro Nakashima, Kazuo Kishi, Paul Martin, Shigeto Seno, Daisuke Okuzaki, Ryoichi Mori

{"title":"Novel integrated multiomics analysis reveals a key role for integrin beta-like 1 in wound scarring.","authors":"Sang-Eun Kim, Ryota Noda, Yu-Chen Liu, Yukari Nakajima, Shoichiro Kameoka, Daisuke Motooka, Seiya Mizuno, Satoru Takahashi, Kento Takaya, Takehiko Murase, Kazuya Ikematsu, Katsiaryna Tratsiakova, Takahiro Motoyama, Masahiro Nakashima, Kazuo Kishi, Paul Martin, Shigeto Seno, Daisuke Okuzaki, Ryoichi Mori","doi":"10.1038/s44319-024-00322-3","DOIUrl":"10.1038/s44319-024-00322-3","url":null,"abstract":"Exacerbation of scarring can originate from a minority fibroblast population that has undergone inflammatory-mediated genetic changes within the wound microenvironment. The fundamental relationship between molecular and spatial organization of the repair process at the single-cell level remains unclear. We have developed a novel, high-resolution spatial multiomics method that integrates spatial transcriptomics with scRNA-Seq; we identified new characteristic features of cell-cell communication and signaling during the repair process. Data from PU.1-/- mice, which lack an inflammatory response, combined with scRNA-Seq and Visium transcriptomics, led to the identification of nine genes potentially involved in inflammation-related scarring, including integrin beta-like 1 (Itgbl1). Transgenic mouse experiments confirmed that Itgbl1-expressing fibroblasts are required for granulation tissue formation and drive fibrogenesis during skin repair. Additionally, we detected a minority population of Acta2high-expressing myofibroblasts with apparent involvement in scarring, in conjunction with Itgbl1 expression. IL1β signaling inhibited Itgbl1 expression in TGFβ1-treated primary fibroblasts from humans and mice. Our novel methodology reveal molecular mechanisms underlying fibroblast-inflammatory cell interactions that initiate wound scarring.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667120","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

The Dystrophin-Dystroglycan complex ensures cytokinesis efficiency in Drosophila epithelia. Dystrophin-Dystroglycan复合体可确保果蝇上皮细胞的细胞分裂效率。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-15 DOI: 10.1038/s44319-024-00319-y

Margarida Gonçalves, Catarina Lopes, Hervé Alégot, Mariana Osswald, Floris Bosveld, Carolina Ramos, Graziella Richard, Yohanns Bellaiche, Vincent Mirouse, Eurico Morais-de-Sá

{"title":"The Dystrophin-Dystroglycan complex ensures cytokinesis efficiency in Drosophila epithelia.","authors":"Margarida Gonçalves, Catarina Lopes, Hervé Alégot, Mariana Osswald, Floris Bosveld, Carolina Ramos, Graziella Richard, Yohanns Bellaiche, Vincent Mirouse, Eurico Morais-de-Sá","doi":"10.1038/s44319-024-00319-y","DOIUrl":"https://doi.org/10.1038/s44319-024-00319-y","url":null,"abstract":"Cytokinesis physically separates daughter cells at the end of cell division. This step is particularly challenging for epithelial cells, which are connected to their neighbors and to the extracellular matrix by transmembrane protein complexes. To systematically evaluate the impact of the cell adhesion machinery on epithelial cytokinesis efficiency, we performed an RNAi-based modifier screen in the Drosophila follicular epithelium. Strikingly, this unveiled adhesion molecules and transmembrane receptors that facilitate cytokinesis completion. Among these is Dystroglycan, which connects the extracellular matrix to the cytoskeleton via Dystrophin. Live imaging revealed that Dystrophin and Dystroglycan become enriched in the ingressing membrane, below the cytokinetic ring, during and after ring constriction. Using multiple alleles, including Dystrophin isoform-specific mutants, we show that Dystrophin/Dystroglycan localization is linked with unanticipated roles in regulating cytokinetic ring contraction and in preventing membrane regression during the abscission period. Altogether, we provide evidence that, rather than opposing cytokinesis completion, the machinery involved in cell-cell and cell-matrix interactions has also evolved functions to ensure cytokinesis efficiency in epithelial tissues.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638468","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

Cultivating the next generation of leaders : How postdocs, principal investigators and institutes can nurture and select for leadership competencies. 培养下一代领导者：博士后、主要研究人员和研究机构如何培养和选拔领导能力。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-12 DOI: 10.1038/s44319-024-00308-1

James W Bryson, Ülkü Uzun, Victor O Oria, Jamie Y Auxillos, Iman Safari, Alexia M Lopresti, Agnieszka Krzyzanowska, Katrine Sonne-Hansen

引用次数: 0

The winter holidays are glorious-except when they're not. 寒假是灿烂的--除了不灿烂的时候。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-11 DOI: 10.1038/s44319-024-00318-z

Shina Caroline Lynn Kamerlin

引用次数: 0

Experience-driven development of decision-related representations in the auditory cortex. 听觉皮层中决策相关表征的经验驱动发展。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-11 DOI: 10.1038/s44319-024-00309-0

Itay Kazanovich, Shir Itzhak, Jennifer Resnik

{"title":"Experience-driven development of decision-related representations in the auditory cortex.","authors":"Itay Kazanovich, Shir Itzhak, Jennifer Resnik","doi":"10.1038/s44319-024-00309-0","DOIUrl":"https://doi.org/10.1038/s44319-024-00309-0","url":null,"abstract":"Associating sensory stimuli with behavioral significance induces substantial changes in stimulus representations. Recent studies suggest that primary sensory cortices not only adjust representations of task-relevant stimuli, but actively participate in encoding features of the decision-making process. We sought to determine whether this trait is innate in sensory cortices or if choice representation develops with time and experience. To trace choice representation development, we perform chronic two-photon calcium imaging in the primary auditory cortex of head-fixed mice while they gain experience in a tone detection task with a delayed decision window. Our results reveal a progressive increase in choice-dependent activity within a specific subpopulation of neurons, aligning with growing task familiarity and adapting to changing task rules. Furthermore, task experience correlates with heightened synchronized activity in these populations and the ability to differentiate between different types of behavioral decisions. Notably, the activity of this subpopulation accurately decodes the same action at different task phases. Our findings establish a dynamic restructuring of population activity in the auditory cortex to encode features of the decision-making process that develop over time and refines with experience.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617010","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

The N-terminal region of DNMT3A engages the nucleosome surface to aid chromatin recruitment. DNMT3A 的 N 端区域与核小体表面接触，帮助染色质招募。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-11 DOI: 10.1038/s44319-024-00306-3

Hannah Wapenaar, Gillian Clifford, Willow Rolls, Moira Pasquier, Hayden Burdett, Yujie Zhang, Gauri Deák, Juan Zou, Christos Spanos, Mark R D Taylor, Jacquie Mills, James A Watson, Dhananjay Kumar, Richard Clark, Alakta Das, Devisree Valsakumar, Janice Bramham, Philipp Voigt, Duncan Sproul, Marcus D Wilson

{"title":"The N-terminal region of DNMT3A engages the nucleosome surface to aid chromatin recruitment.","authors":"Hannah Wapenaar, Gillian Clifford, Willow Rolls, Moira Pasquier, Hayden Burdett, Yujie Zhang, Gauri Deák, Juan Zou, Christos Spanos, Mark R D Taylor, Jacquie Mills, James A Watson, Dhananjay Kumar, Richard Clark, Alakta Das, Devisree Valsakumar, Janice Bramham, Philipp Voigt, Duncan Sproul, Marcus D Wilson","doi":"10.1038/s44319-024-00306-3","DOIUrl":"https://doi.org/10.1038/s44319-024-00306-3","url":null,"abstract":"DNA methyltransferase 3A (DNMT3A) plays a critical role in establishing and maintaining DNA methylation patterns in vertebrates. Here we structurally and biochemically explore the interaction of DNMT3A1 with diverse modified nucleosomes indicative of different chromatin environments. A cryo-EM structure of the full-length DNMT3A1-DNMT3L complex with a H2AK119ub nucleosome reveals that the DNMT3A1 ubiquitin-dependent recruitment (UDR) motif interacts specifically with H2AK119ub and makes extensive contacts with the core nucleosome histone surface. This interaction facilitates robust DNMT3A1 binding to nucleosomes, and previously unexplained DNMT3A disease-associated mutations disrupt this interface. Furthermore, the UDR-nucleosome interaction synergises with other DNMT3A chromatin reading elements in the absence of histone ubiquitylation. H2AK119ub does not stimulate DNMT3A DNA methylation activity, as observed for the previously described H3K36me2 mark, which may explain low levels of DNA methylation on H2AK119ub marked facultative heterochromatin. This study highlights the importance of multivalent binding of DNMT3A to histone modifications and the nucleosome surface and increases our understanding of how DNMT3A1 chromatin recruitment occurs.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617053","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

Palmitoylation by ZDHHC4 inhibits TRPV1-mediated nociception. ZDHHC4 的棕榈酰化抑制了 TRPV1 介导的痛觉。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-11 DOI: 10.1038/s44319-024-00317-0

Youjing Zhang, Mengyu Zhang, Cheng Tang, Junyan Hu, Xufeng Cheng, Yang Li, Zefeng Chen, Yuan Yin, Chang Xie, Dongdong Li, Jing Yao

引用次数: 0