{"id":18,"title":"Self-organization of Drosophila chromatin architecture in a cell-free system","title_zh":"无细胞体系中果蝇染色质三维结构的自组织重建","url":"https://pubmed.ncbi.nlm.nih.gov/42972103","doi":"10.1038/s44319-026-00969-0","pmid":"42972103","journal":"EMBO Rep","kind":"paper","lang":"en","published_at":"2026-11-02T00:00:00+00:00","fetched_at":"2026-11-08T03:43:49+00:00","authors":["Jayakrishnan M","Kars G","Campos-Sparr A","Karpinska MA","Zunjarrao S","Maziak N","Margulies CE","Vaquerizas JM","Gambetta MC","Oudelaar AM","Becker PB"],"primary_topic":"repro-genetics","topics":[{"slug":"repro-genetics","score":5.0,"hits":["3d genome","chromatin architecture"]},{"slug":"animal-models","score":3.2,"hits":["drosophila"]},{"slug":"early-embryo","score":1.0,"hits":["early embryos"]},{"slug":"ethics-policy","score":1.0,"hits":["regulatory"]}],"topic_score":5.0,"preference_score":8.0,"preference_labels":["早期胚胎表观基因组 / 染色质"],"llm_score":63.0,"final_score":71.0,"score_dims":{"novelty":85,"rigor":78,"impact":58,"relevance":32,"translation":18},"recommend_reason":"在无细胞体系中重建染色质折叠并用 Micro-C 解析，方法学新颖，对理解早期胚胎染色质结构起源（转录沉默期的原始折叠）有概念性价值；但对象为果蝇合胞体胚胎提取物，与人类 ART 和临床决策距离较远，更偏基础染色质生物学。","keywords":["染色质三维结构","TAD","无细胞体系","Micro-C","Su(Hw)绝缘子","果蝇早期胚胎"],"selected":1,"story_id":213,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-embryo-omics","source_name":"PubMed · 胚胎/卵母细胞组学","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"该研究利用果蝇合胞体胚胎提取物建立了体外重建复杂染色质的无细胞体系，通过核小体定位与 Micro-C 分析发现，远距离互作（包括顺式/反式环与 TAD）可由可溶性提取物组分自发形成；部分结构与早期胚胎中观察到的结构相似，另一些则是在体内受到约束的潜在互作势能。针对 eve 位点，作者发现 TAD 形成无法用简单环挤出模型解释，而需要绝缘子蛋白 Su(Hw) 介导的边界元件直接配对。结论：三维基因组组织的关键特征可在无细胞体系中重建，为机制解析提供可用平台。","summary":"Metazoan genomes are organized by folding of the nucleosome fiber into loops and domains that support long-range regulatory interactions. Although cohesin-mediated loop extrusion and architectural DNA-binding proteins are central to current models of genome organization, how these mechanisms integrate to generate higher-order structure remains incompletely understood. Early Drosophila melanogaster embryogenesis provides a unique window into the emergence of chromatin architecture, as rapid syncytial nuclear divisions occur largely in the absence of transcription. However, probing the mechanisms underlying this primordial folding in vivo is technically challenging. Here, we establish an in vitro system that reconstitutes complex chromatin using extracts from syncytial embryos. Nucleosome mapping and Micro-C analyses reveal that long-range interactions, including cis and trans loops and topologically associating domains (TADs), emerge spontaneously from soluble extract components. While some structures resemble those observed in early embryos, others represent latent interaction potentials that are constrained in vivo. Focusing on the eve locus, we find that TAD formation is incompatible with a simple loop extrusion model and instead requires direct pairing of boundary elements mediated by the insulator protein 'Suppressor-of-hairy-wing' Su(Hw). Together, our work demonstrates that key features of 3D genome organization can be reconstituted in a cell-free system and provides a tractable platform for the mechanistic dissection of chromatin folding in Drosophila.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}