{"id":353,"title":"A TORC1-regulated H3K4me reader preserves promoter chromatin stability, and its degradation promotes meiotic remodeling","title_zh":"TORC1 调控的 H3K4me 阅读蛋白维持启动子染色质稳定，其降解促进减数分裂重塑","url":"https://pubmed.ncbi.nlm.nih.gov/42976865","doi":"10.1016/j.molcel.2026.10.013","pmid":"42976865","journal":"Mol Cell","kind":"paper","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Yun L","Zhang PC","Zhou K","Wang WT","Zhang KY","Wu YL","Zhu M","Ge HQ","Min T","Suo F","Du LL","Guo W","Sun LL","Wei Y"],"primary_topic":"oocyte","topics":[{"slug":"oocyte","score":4.0,"hits":["meiotic"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":64.0,"final_score":72.0,"score_dims":{"novelty":82,"rigor":85,"impact":60,"relevance":32,"translation":18},"recommend_reason":"机制新颖、实验体系严谨，揭示 TORC1 通过降解 H3K4me 阅读蛋白驱动启动子染色质程序性重塑并启动减数分裂，对理解减数分裂进入的染色质调控有参考价值；但研究对象为裂殖酵母，与人类生殖及 ART 临床距离较远，属基础机制旁证。","keywords":["TORC1","H3K4 甲基化","Jmj3/Lid2","启动子染色质","减数分裂","NuA4"],"selected":1,"story_id":129,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":3,"has_interpretation":false,"journal_key":"mol-cell","journal_tier":"cns-sub","journal_if":14.5,"is_mock":false,"summary_zh":"本研究在裂殖酵母中揭示：必需基因 jmj3 与 lid2 编码的蛋白协同限制 H3K4me 依赖的 NuA4 乙酰转移酶在启动子染色质上的异常募集，从而抑制 H4 过度乙酰化、SWI/SNF 介导的重塑以及启动子区核小体大小脆弱颗粒（NSFP）的不稳定，维持营养生长所需的转录程序。营养限制时，TORC1 失活触发 Ubc14-Dbl4 依赖的 Jmj3 与 Lid2 降解，导致程序性启动子重塑；Jmj3/Lid2 缺失将减数分裂转录重编程与 Rec12 依赖的重组热点激活相偶联，保障减数分裂分化效率。研究提出营养响应性的染色质保护—重塑转换机制。","summary":"Histone H3 lysine 4 methylation (H3K4me) is enriched at active promoters and promotes the recruitment of chromatin regulators, yet how cells protect H3K4-methylated promoter chromatin from inappropriate remodeling remains unknown. Here, we show that proteins encoded by the essential genes jmj3 and lid2 in fission yeast function coordinately to preserve promoter chromatin stability by limiting inappropriate H3K4me-dependent NuA4 acetyltransferase chromatin engagement. Decreased NuA4 at the chromatin restricts excessive histone H4 acetylation, SWI/SNF-mediated remodeling, and promoter-associated nucleosome-sized fragile particle (NSFP) destabilization, thereby maintaining transcriptional programs that support vegetative growth. Upon nutrient limitation, TOR complex 1 (TORC1) inactivation triggers Ubc14-Dbl4-dependent degradation of Jmj3 and Lid2, which results in programmed promoter remodeling. Moreover, loss of Jmj3/Lid2 couples meiotic transcriptional reprogramming with Rec12-dependent recombination hotspot activation, ensuring efficient meiotic differentiation. Together, our findings identify a nutrient-responsive mechanism that safeguards H3K4-methylated promoter chromatin while permitting regulated chromatin remodeling during developmental transition.","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}}