近日,美国怀特黑德生物医学研究所Richard A. Young与Rudolf Jaenisch等研究人员合作发现,MeCP2调控异染色质相分离与神经发育疾病。该研究于2020年7月22日在线发表于《自然》。
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
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html
本期文章:《自然》:Online/在线发表