MeCP2調控異染色質相分離
作者：
小柯機器人發布時間：2020/7/23 14:05:00
近日，美國懷特黑德生物醫學研究所Richard A. Young與Rudolf Jaenisch等研究人員合作發現，MeCP2調控異染色質相分離與神經發育疾病。該研究於2020年7月22日在線發表於《自然》。
據研究人員介紹，MeCP2（甲基CpG結合蛋白2）是組成型異染色質的關鍵組成部分，在染色體維持和轉錄沉默中起重要作用。MeCP2的突變會引起Rett症候群（RTT），這是一種出生後的進行性神經發育障礙，與嚴重的智力殘疾和自閉症樣症狀相關，並在兒童早期就表現出來。長期以來被認為是緻密且相對靜態的異染色質現在被認為表現出與液體狀冷凝物一致的性質。
研究人員發現，MeCP2是細胞中異染色質濃縮物的動態成分，並受DNA刺激形成液體狀的冷凝物。該蛋白包含有助於形成冷凝物的多個結構域，並且與轉錄活性濃縮物成分相比，其表現出選擇性濃縮異染色質輔因子的理化特性。
此外，因RTT突變而引起改變時，其形成冷凝物的能力也會受到破壞。研究人員認為，MeCP2通過其冷凝物分配特性增強異染色質/常染色質分離，並且冷凝物破壞可能是RTT患者突變的常見結果。
附：英文原文
Title: MeCP2 links heterochromatin condensates and neurodevelopmental disease
Author: Charles H. Li, Eliot L. Coffey, Alessandra DallAgnese, Nancy M. Hannett, Xin Tang, Jonathan E. Henninger, Jesse M. Platt, Ozgur Oksuz, Alicia V. Zamudio, Lena K. Afeyan, Jurian Schuijers, X. Shawn Liu, Styliani Markoulaki, Tenzin Lungjangwa, Gary LeRoy, Devon S. Svoboda, Emile Wogram, Tong Ihn Lee, Rudolf Jaenisch, Richard A. Young
Issue&Volume: 2020-07-22
Abstract: MeCP2 (methyl CpG binding protein 2) is a key component of constitutive heterochromatin, which plays important roles in chromosome maintenance and transcriptional silencing1–3. Mutations in MeCP2 cause Rett syndrome (RTT)3–5, a postnatal progressive neurodevelopmental disorder associated with severe mental disability and autism-like symptoms that manifests in girls during early childhood. Heterochromatin, long considered a dense and relatively static structure1,2, is now understood to exhibit properties consistent with a liquid-like condensate6,7. Here we report that MeCP2 is a dynamic component of heterochromatin condensates in cells, is stimulated by DNA to form liquid-like condensates, contains multiple domains that contribute to condensate formation, manifests physicochemical properties that selectively concentrate heterochromatin cofactors compared to components of transcriptionally active condensates, and when altered by RTT-causing mutations is disrupted in its ability to form condensates. We propose that MeCP2 enhances heterochromatin/euchromatin separation through its condensate partitioning properties and that condensate disruption may be a common consequence of mutations found in patients with RTT.
DOI: 10.1038/s41586-020-2574-4
Source: https://www.nature.com/articles/s41586-020-2574-4