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High-performance n-type flexible inorganic thermoelectric aerogel for energy harvesting. 用于能量收集的高性能n型柔性无机热电气凝胶。
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.ady7679
Xiaodong Wang,Wenbo Zhu,Yijie Liu,Shuaihang Hou,Li Yin,Jinxuan Cheng,Peng Zhao,Feng Jiang,Sichen Duan,Wenhua Xue,Yumei Wang,Xuesong Leng,Feng Cao,Jun Mao,Mingyu Li,Qian Zhang
Despite their promise as lightweight, ultralow-thermal-conductivity thermoelectric (TE) materials, aerogels have been largely limited to p-type organic or carbon-based systems with modest zT < 0.1 at 300 kelvin. Here, we propose a stepwise synthesis strategy that yields the first inorganic aerogel exhibiting state-of-the-art n-type TE performance. Optimized aerogels with 95% porosity exhibit a high power factor of 34.8 microwatts per meter per square kelvin and an ultralow thermal conductivity of 0.061 microwatts per meter per kelvin, resulting in zT values of 0.17 at 300 kelvin and 0.24 at 383 kelvin. A vertical TE generator prototype with six TE-aerogel legs achieves a gravimetric output power of 76 microwatts per gram under a ΔT of ~60 kelvin. To address brittleness, a polyimide-encapsulated aerogel with bioinspired architecture was developed, achieving a high compressive strength to 1.4 kilopascals while maintaining excellent TE performance. This work establishes a generalizable method for designing high-performance flexible inorganic aerogels, opening more possibilities for lightweight wearable energy harvesting technologies.
尽管它们有望成为轻质、超低导热的热电(TE)材料,但气凝胶在很大程度上仅限于在300开尔文时zT < 0.1的p型有机或碳基体系。在这里,我们提出了一种逐步合成策略,产生了第一个具有最先进n型TE性能的无机气凝胶。优化后的气凝胶孔隙率为95%,其功率因数为34.8微瓦/米/平方开尔文,导热系数为0.061微瓦/米/开尔文,在300开尔文时zT值为0.17,在383开尔文时zT值为0.24。在ΔT ~60开氏度的条件下,具有6个TE气凝胶腿的垂直TE发电机原型可以实现每克76微瓦的重力输出功率。为了解决脆性问题,开发了一种具有生物启发结构的聚酰亚胺封装气凝胶,在保持优异TE性能的同时,实现了高达1.4千帕的高抗压强度。这项工作为设计高性能柔性无机气凝胶建立了一种可推广的方法,为轻量级可穿戴能量收集技术开辟了更多的可能性。
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引用次数: 0
Mass extinction triggered the early radiations of jawed vertebrates and their jawless relatives (gnathostomes) 大灭绝引发了有颌脊椎动物及其无颌近亲(颌口动物)的早期辐射。
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.aeb2297
Wahei Hagiwara, Lauren Sallan
Most vertebrate lineages are first recorded from the mid-Paleozoic, well after their Cambrian origin and Ordovician invertebrate biodiversification events. This delay has been poorly understood and is usually attributed to sampling and long ghost lineages. We analyzed newly compiled databases of Paleozoic vertebrate occurrences, biogeography, and ecosystems, revealing that the Late Ordovician Mass Extinction (~445 to 443 million years ago) triggered parallel, endemic radiations of jawed and related jawless vertebrates (gnathostomes) in isolated refugia. Postextinction ecosystems hosted the first definitive appearances of most major vertebrate lineages of the Paleozoic “Age of Fishes” (and today), following the loss of ubiquitous stem-cyclostome conodonts, nascent faunas of other gnathostomes, and pelagic invertebrates. Turnover and recovery patterns matched those following climatically similar events like the end-Devonian mass extinction, including a postextinction “gap” with low biodiversity. The prolonged Silurian recovery, and the challenges of oceanic dispersal, likely further delayed the dominance of jawed gnathostomes for millions of years after the first fossil jaws.
大多数脊椎动物谱系最早记录于中古生代,远晚于它们的寒武纪起源和奥陶纪无脊椎动物生物多样化事件。人们对这种延迟知之甚少,通常将其归因于采样和长鬼魂血统。我们分析了古生代脊椎动物、生物地理学和生态系统的新数据库,揭示了晚奥陶纪大灭绝(约4.45亿至4.43亿年前)在孤立的避难所引发了有颌和相关无颌脊椎动物(颌口动物)的平行、地方性辐射。灭绝后的生态系统孕育了古生代“鱼类时代”(以及今天)大多数主要脊椎动物谱系的首次明确出现,随后是无处不在的茎环形牙形刺、其他啮齿动物的新生动物群和远洋无脊椎动物的消失。更替和恢复模式与气候相似的事件相匹配,如泥盆纪末的大灭绝,包括生物多样性低的灭绝后“间隙”。志留纪的长期恢复,以及海洋扩散的挑战,可能进一步推迟了颌口动物在第一个颌骨化石之后的数百万年的统治地位。
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引用次数: 0
GluN2B-specific NMDAR positive allosteric modulation reverses cognitive and behavioral abnormalities in Mecp2 and Disc1 transgenic mice. glun2b特异性NMDAR阳性变构调节可逆转Mecp2和Disc1转基因小鼠的认知和行为异常。
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.ady3891
Yang Ge,Tian Tian,Bolong Li,Peter Axerio-Cillies,Wenlin Chen,Xin Qin,Mudi Zhao,Qi-Cheng Sun,Jiaqi Li,Stan B Floresco,Lidong Liu,Xin Yang,Yu Tian Wang
The GluN2B subunit of N-methyl-d-aspartate receptors (NMDARs) plays a central role in synaptic development and plasticity, and its hypofunction is linked to autism spectrum disorder (ASD), severe neurodevelopmental delay, and other neuropsychiatric diseases. Therefore, enhancing the function of this NMDAR subunit may provide an effective therapeutic strategy for correcting synaptic and behavioral deficits associated with GluN2B hypofunction. Here, we developed a class of GluN2B-selective positive allosteric modulators and characterized the pharmacological properties and binding site of the lead compound, 175. Systemic application of 175 facilitates hippocampal long-term depression in rats. 175 restores performances in open-field exploration and three-chamber test in Mecp2 overexpression mice that exhibit GluN2B hypofunction and autism-like features. Treatment with 175 also reverses behavioral abnormalities in open-field, Y-maze spontaneous alternation, three-chamber test, and prepulse inhibition in Disc1 mutant mice. Our findings introduce a pharmacological tool for selectively potentiating GluN2B-NMDAR function and highlight its therapeutic potential for cognitive and behavioral symptoms associated with GluN2B hypofunction.
n -甲基-d-天冬氨酸受体(NMDARs)的GluN2B亚基在突触发育和可塑性中起核心作用,其功能障碍与自闭症谱系障碍(ASD)、严重神经发育迟缓和其他神经精神疾病有关。因此,增强该NMDAR亚基的功能可能为纠正与GluN2B功能减退相关的突触和行为缺陷提供有效的治疗策略。在这里,我们开发了一类glun2b选择性阳性变构调节剂,并表征了先导化合物175的药理学性质和结合位点。175对大鼠海马长期抑郁有促进作用。175可以恢复Mecp2过表达小鼠的开放性探索和三室实验的表现,这些小鼠表现出GluN2B功能低下和自闭症样特征。175治疗还能逆转Disc1突变小鼠在野外、y迷宫自发交替、三室试验和脉冲前抑制中的行为异常。我们的研究结果介绍了一种选择性增强GluN2B- nmdar功能的药理学工具,并强调了其治疗与GluN2B功能减退相关的认知和行为症状的潜力。
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引用次数: 0
Improved air-sea CO2 flux estimates from sailboat measurements. 改进了通过帆船测量估算大气-海洋二氧化碳通量。
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.adz1502
Jacqueline Behncke,Tatiana Ilyina,Fatemeh Chegini,Peter Landschützer
Despite their importance in the climate system, remote ocean regions and their ability to absorb anthropogenic carbon dioxide (CO2) remain highly uncertain. To address this issue, citizen science initiatives, including sailboats, expand the observational network. Using observing system simulations and novel sailboat tracks, we demonstrate how integrating sailboat data improves estimates of ocean carbon uptake. While we underestimate the ocean carbon sink when mimicking real-world sampling, adding available sailboat data does not substantially improve reconstructions. Nevertheless, increased sampling reveals a stronger carbon sink, particularly between 40°S and 60°S. The improvement persists with hypothetical measurement uncertainties, but substantial differences arise depending on whether positive or negative biases are applied to the race track data. While we show that two additional circumnavigations already improve the ocean mean sink estimate, we further highlight the finding that the additional data remain insufficient to correct the overestimated CO2 sink trend, calling for continuation of the ongoing data collection.
尽管它们在气候系统中很重要,但遥远的海洋区域及其吸收人为二氧化碳的能力仍然高度不确定。为了解决这个问题,公民科学计划,包括帆船,扩大了观测网络。利用观测系统模拟和新颖的帆船轨迹,我们展示了整合帆船数据如何改善海洋碳吸收的估计。虽然我们在模拟真实世界的采样时低估了海洋碳汇,但添加可用的帆船数据并不能从本质上改善重建结果。然而,增加采样显示碳汇更强,特别是在40°S和60°S之间。这种改进在假设的测量不确定性下仍然存在,但根据对赛道数据应用的是积极的还是消极的偏差,会产生实质性的差异。虽然我们表明,额外的两次环球航行已经改善了海洋平均汇的估计,但我们进一步强调,额外的数据仍然不足以纠正高估的二氧化碳汇趋势,呼吁继续进行正在进行的数据收集。
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引用次数: 0
Highly efficient α-sialylation with ortho-(1-phenylvinyl)benzoates as leaving groups: One-pot assembly of α-sialoglycans. 邻苯二甲酸酯作为离去基的高效α-唾液酰化:α-唾液聚糖的一锅组装。
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.aeb0711
Yunqin Zhang,Yujie Ji,Qiang Tan,Hanyingzi Fan,Qingli Zhou,Caixia Yin,Siqi Li,Xiufang Wang,Gang Lu,Guozhi Xiao
Sialic acid represents one of the most important monosaccharides in mammals. However, because of the unique structure of sialic acid with the anomeric center flanked by methylene and carboxyl groups, efficient synthetic access to sialoglycans remains a difficult task, thus hindering in-depth biological studies. Here, we report one-pot α-sialylation protocol for efficient synthesis of various α-sialoglycans, using sialyl ortho-(1-phenylvinyl)benzoates (PVB) as donors. This α-sialylation method enjoys broad substrate scope and high yields. In particular, this α-sialylation protocol has been successfully applied in one-pot synthesis of several α-sialoglycans, including bioactive ganglioside Hp-s1 and STN antigen with reduced steps and improved efficiency. Furthermore, density functional theory calculations provide the mechanistic insights of much higher reactivity of sialyl PVB donors than the corresponding thiosialoside donors in the presence of N-iodosuccinimide (NIS) and trifluoromethanesulfonic acid (TfOH). The enhanced reactivity arises from favorable noncovalent interactions and effective stabilization of the carbocation intermediate by the two phenyl groups within the PVB moieties.
唾液酸是哺乳动物体内最重要的单糖之一。然而,由于唾液酸的独特结构,其中心被亚甲基和羧基包围,有效地合成唾液聚糖仍然是一项艰巨的任务,从而阻碍了深入的生物学研究。在这里,我们报道了一锅α-唾液化方案,有效合成各种α-唾液聚糖,使用唾液基邻苯乙烯基苯甲酸酯(PVB)作为供体。该α-唾液酰化方法底物范围广,收率高。特别是,该α-唾液酰化方案已成功应用于几种α-唾液聚糖的一锅合成,包括生物活性神经节苷脂Hp-s1和STN抗原,减少了步骤,提高了效率。此外,密度泛函理论计算提供了在n -碘丁二酰亚胺(NIS)和三氟甲烷磺酸(TfOH)存在下,硅基PVB给体的反应活性比相应的硫代硅苷给体高得多的机理见解。增强的反应活性源于良好的非共价相互作用和PVB基团内的两个苯基对碳正离子中间体的有效稳定。
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引用次数: 0
Molecular computation at equilibrium via programmable entropy 通过可编程熵的分子平衡计算
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.adx3969
Boya Wang, Cameron Chalk, David Doty, David Soloveichik
Synthetic molecular information processing is typically designed through programming kinetic pathways, so that molecules bind, unbind, or incur conformational changes in some desired order. We demonstrate an alternative paradigm in dynamic DNA nanotechnology that programs the thermodynamic equilibrium state directly, with computation emerging from entropic driving forces. Like declarative programming in computer science, this approach emphasizes desired outcomes rather than specific steps, simplifying molecular programming and avoiding errors caused when thermodynamic forces work against programmed kinetics. We show broad applicability through three distinct applications: reversible signal propagation with fan-in and fan-out, algorithmic self-assembly performing Boolean logic, and synthesis of molecular chains (concatemers) of programmable length, illustrating how thermodynamic computation can enable practical molecular engineering tasks. Our work may enable previously unexplored ways to engineer complex molecular behaviors and help inform the understanding of the computational power of thermodynamics versus kinetics for molecular systems.
合成分子信息处理通常是通过编程动力学途径来设计的,因此分子结合、解结合或引起某种期望顺序的构象变化。我们展示了动态DNA纳米技术的另一种范例,即直接编程热力学平衡状态,计算来自熵驱动力。就像计算机科学中的声明式编程一样,这种方法强调期望的结果,而不是具体的步骤,简化了分子编程,避免了热力学力与程序动力学相抵触时造成的错误。我们通过三个不同的应用展示了广泛的适用性:扇入和扇出的可逆信号传播,执行布尔逻辑的算法自组装,以及可编程长度的分子链(串联体)的合成,说明了热力学计算如何能够实现实际的分子工程任务。我们的工作可能使以前未探索的方法来设计复杂的分子行为,并有助于了解分子系统热力学与动力学的计算能力。
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引用次数: 0
Anode-induced arylthiol-amine cross-coupling: A nontraditional strategy to access sulfinamides. 阳极诱导芳基硫醇-胺交叉偶联:一种获取亚胺的非传统策略。
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.aeb6913
Pan Zhou,Ting Zou,Sen-Hui Wu,Hong-Jian Song,Yu-Xiu Liu,Qing-Min Wang
Sulfinamides are ubiquitous structures among natural products and biologically active compounds. Generic synthetic methods for sulfinamides remain elusive because the preparation of sulfoxide precursors is notoriously difficult. Direct construction of S─N bonds represents a highly efficient economical method to access these sulfinamides. However, the most prevalent techniques for their synthesis are still the nonradical approaches of sulfoxide precursors with amines, where prepreparation of substrates, harsh reaction conditions, and restricted substrate ranges have intrinsically limited the synthetic scope. Herein, we leveraged a practical and streamlined electrocatalytic strategy to achieve sulfinamide synthesis, which involves the intermolecular oxidative cross-coupling of readily available arylthiols and aliphatic amines. Mechanistic investigations indicate that four successive oxidations at the anode play a crucial role in radical generation, S─N bond formation, and further oxidation of intermediates.
亚胺类化合物是天然产物和生物活性化合物中普遍存在的结构。亚砜的通用合成方法仍然难以捉摸,因为亚砜前体的制备是出了名的困难。直接构建S─N键是获得这些亚胺的一种高效经济的方法。然而,目前合成亚砜的最普遍的技术仍然是含胺的亚砜前体的非自由基方法,其中底物的预制备、苛刻的反应条件和有限的底物范围从本质上限制了合成范围。在这里,我们利用一种实用的、流线型的电催化策略来实现亚砜酰胺的合成,这涉及到容易获得的芳基硫醇和脂肪胺的分子间氧化交叉偶联。机理研究表明,在阳极上连续发生的四次氧化在自由基生成、S─N键形成和中间产物的进一步氧化中起着至关重要的作用。
{"title":"Anode-induced arylthiol-amine cross-coupling: A nontraditional strategy to access sulfinamides.","authors":"Pan Zhou,Ting Zou,Sen-Hui Wu,Hong-Jian Song,Yu-Xiu Liu,Qing-Min Wang","doi":"10.1126/sciadv.aeb6913","DOIUrl":"https://doi.org/10.1126/sciadv.aeb6913","url":null,"abstract":"Sulfinamides are ubiquitous structures among natural products and biologically active compounds. Generic synthetic methods for sulfinamides remain elusive because the preparation of sulfoxide precursors is notoriously difficult. Direct construction of S─N bonds represents a highly efficient economical method to access these sulfinamides. However, the most prevalent techniques for their synthesis are still the nonradical approaches of sulfoxide precursors with amines, where prepreparation of substrates, harsh reaction conditions, and restricted substrate ranges have intrinsically limited the synthetic scope. Herein, we leveraged a practical and streamlined electrocatalytic strategy to achieve sulfinamide synthesis, which involves the intermolecular oxidative cross-coupling of readily available arylthiols and aliphatic amines. Mechanistic investigations indicate that four successive oxidations at the anode play a crucial role in radical generation, S─N bond formation, and further oxidation of intermediates.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"15 1","pages":"eaeb6913"},"PeriodicalIF":13.6,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NIR-switched DNA tweezer enables reversible miRNA recognition with erasable signal for in vivo continuous imaging. nir开关的DNA镊子使可逆性miRNA识别具有可擦除信号,用于体内连续成像。
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.adz3560
Caixia Wang,Yulin Cong,Linlin Yang,Liang Liu,Yuxin Xie,Xuan Ding,Guixiang Zeng,Huangxian Ju,Ying Liu
Continuous monitoring of miRNA expression in vivo is crucial for understanding complex biological processes. However, current miRNA imaging probes suffer from irreversible responses, impairing their capabilities for real-time tracking concentration fluctuations. Here, we present a near-infrared regulated DNA tweezer (NIR-DNA tweezer) with reversible binding affinities to target miRNA. Self-quenched DNA tweezer is composed of BHQ3-labeled miRNA recognition strand and Cy5-labeled competitive strand, while competitive strand is embedded with azobenzene (Azo) to photo-switch the hybridization zones of DNA tweezer for reversible miRNA recognitions. NIR-DNA tweezer is obtained by conjugating DNA tweezer to upconversion nanoparticles, which is switched to "transit" status upon high-power 808-nm irradiation with cis-Azo to allow miRNA recognition with Cy5 fluorescence recovery. Upon low-power 808-nm irradiation, NIR-DNA tweezer is switched to "closed" status with trans-Azo to release miRNA and erase signal. The as-presented NIR-DNA tweezer achieves real-time in vivo tracing of miRNA expression fluctuations upon continuous chemotherapeutic drug and inhibitor treatments.
持续监测miRNA在体内的表达对于理解复杂的生物过程至关重要。然而,目前的miRNA成像探针受到不可逆反应的影响,削弱了它们实时跟踪浓度波动的能力。在这里,我们提出了一种近红外调节的DNA镊子(NIR-DNA镊子),具有与目标miRNA的可逆结合亲和力。自猝灭DNA镊子由bhq3标记的miRNA识别链和cy5标记的竞争链组成,竞争链嵌入偶氮苯(Azo),光开关DNA镊子的杂交区,进行可逆的miRNA识别。NIR-DNA镊子是通过将DNA镊子与上转换纳米颗粒偶联得到的,在顺式偶氮高功率808 nm照射下,纳米颗粒切换到“转运”状态,允许用Cy5荧光恢复识别miRNA。在低功率808 nm照射下,NIR-DNA镊子与反式偶氮切换到“关闭”状态,释放miRNA并擦除信号。本文提出的NIR-DNA镊子实现了持续化疗药物和抑制剂治疗时miRNA表达波动的实时体内追踪。
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引用次数: 0
Genomic adaptation strategies to habitat switching in Korarchaeota. Korarchaeota生境转换的基因组适应策略。
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.aea1035
Lei Su,Andreas P Teske,Ian P G Marshall,Zichao Zeng,Yinzhao Wang,Kurt O Konhauser,Yuhao Li,Shengwei Hou,Jiangtao Li
Korarchaeota, an ancient lineage of archaea, has long been overlooked in discussions of archaeal and eukaryotic evolution. Their physiology and evolutionary history have remained enigmatic due to their rarity in natural environments. Here, we assembled 101 Korarchaeota genomes from different seafloor hydrothermal vents and terrestrial hot springs, revealing that Korarchaeota lineages have undergone multiple transitions between marine and terrestrial habitats. These transitions were accompanied by genomic shifts reflecting adaptations to habitat-specific physicochemical conditions, including variations in nutrient availability, potential energy sources, osmotic conditions, and viral predation stresses. Molecular dating suggests that Korarchaeota originated ~2.84 billion years (Ga) ago, with three subsequent diversification events occurring around 2.42, 1.52, and 1.29 Ga ago. These major diversifications coincide with key geological events such as the Great Oxidation Event and the breakup and formation of supercontinents. Our findings provide insights into the evolutionary trajectory and ecological adaptations of Korarchaeota, thereby enhancing our understanding of microbial coevolution with Earth's dynamic surface environments.
古细菌是古细菌的一个古老谱系,在古细菌和真核生物进化的讨论中一直被忽视。由于它们在自然环境中的稀少,它们的生理和进化历史一直是个谜。本文对来自不同海底热液喷口和陆地温泉的101个Korarchaeota基因组进行了组装,揭示了Korarchaeota谱系在海洋和陆地栖息地之间经历了多次转变。这些转变伴随着基因组的变化,反映了对栖息地特定物理化学条件的适应,包括营养可用性、潜在能量来源、渗透条件和病毒捕食压力的变化。分子测年表明,Korarchaeota起源于~ 28.4亿Ga前,随后的三次多样化事件分别发生在2.42、1.52和1.29 Ga前。这些主要的多样化与重要的地质事件相吻合,如大氧化事件和超级大陆的分裂和形成。我们的研究结果提供了对Korarchaeota的进化轨迹和生态适应的见解,从而增强了我们对微生物与地球动态表面环境共同进化的理解。
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引用次数: 0
Basis for lineage-determining pioneer factors targeting distinct repressed chromatin states. 针对不同抑制染色质状态的谱系决定先驱因子的基础。
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-09 DOI: 10.1126/sciadv.adz7409
Andrew Katznelson,Jingchao Zhang,Greg Donahue,Kenneth S Zaret
Pioneer transcription factors target transcriptionally silent chromatin, thereby enabling gene activation in development, regeneration, and cell reprogramming. However, silent chromatin is heterogeneous, varying in nucleosome stability, nucleosome compaction, and repressive histone modifications, and how pioneer factors may differentially overcome these different chromatin barriers is unknown. We systematically compared the chromatin targeting of 13 embryonic transcription factors and found that the DNA binding domain (DBD) type predicts whether a pioneer factor targets low-turnover nucleosomes in compact chromatin, dynamic nucleosomes in compact chromatin or functions as a nonpioneer factor targeting accessible chromatin. By contrast, non-DBD domains enable targeting of repressed chromatin marked by H3K9me3 or H3K27me3. Fusions of different non-DBD segments of heterochromatin-targeting pioneer factors to the transcription factor SOX2 can expand binding of SOX2 target motifs within heterochromatin and improve cellular reprogramming. Our study unveils how different forms of silent chromatin are coordinately targeted by lineage-specifying factors.
先锋转录因子靶向转录沉默的染色质,从而在发育、再生和细胞重编程中激活基因。然而,沉默的染色质是异质的,在核小体稳定性、核小体压实和抑制性组蛋白修饰方面各不相同,而先锋因子如何以不同的方式克服这些不同的染色质屏障尚不清楚。我们系统地比较了13种胚胎转录因子的染色质靶向,发现DNA结合域(DBD)类型预测了一个先锋因子是靶向致密染色质中的低周转率核小体、致密染色质中的动态核小体,还是作为一个非先锋因子靶向可接近的染色质。相比之下,非dbd结构域能够靶向由H3K9me3或H3K27me3标记的受抑制染色质。将异染色质靶向先驱因子的不同非dbd片段与转录因子SOX2融合,可以扩大SOX2靶基在异染色质内的结合,改善细胞重编程。我们的研究揭示了不同形式的沉默染色质是如何被谱系指定因子协调靶向的。
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引用次数: 0
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