小柯机器人

美国马萨诸塞州总医院和哈佛医学院Miguel N. Rivera团队近期取得重要工作进展，他们研究利用DisP-seq揭示DNA相关无序蛋白质的全基因组功能组织。相关研究成果2023年4月10日在线发表于《自然—生物技术》杂志上。

据介绍，已知DNA相关蛋白中的固有无序区（IDR）会影响基因调控，但它们在全基因组调控程序中的分布和协同功能仍知之甚少。

研究人员提出了DisP-seq（无序蛋白质沉淀，然后进行DNA测序），这是一种不依赖抗体的化学沉淀分析方法，可以通过生物素化异恶唑沉淀和下一代测序的组合，同时绘制内源性DNA相关无序蛋白质的全基因组图。DisP-seq图谱由数千个与不同染色质状态相关的峰组成，富含无序转录因子（TF），并且通常排列在具有高局部浓度的无序蛋白和与调节潜力相关的组蛋白修饰的不同组合的大谱系特异性簇中。

总之，研究人员使用DisP-seq分析癌症细胞，并揭示无序蛋白相关岛如何使IDR依赖机制能够控制无序TF的结合和功能，包括TF通过长程相互作用的癌基因依赖性隔离，以及在尤因肉瘤中失去致癌刺激后再激活分化途径。

附：英文原文

Title: DisP-seq reveals the genome-wide functional organization of DNA-associated disordered proteins

Author: Xing, Yu-Hang, Dong, Rui, Lee, Lukuo, Rengarajan, Shruthi, Riggi, Nicol, Boulay, Gaylor, Rivera, Miguel N.

Issue&Volume: 2023-04-10

Abstract: Intrinsically disordered regions (IDRs) in DNA-associated proteins are known to influence gene regulation, but their distribution and cooperative functions in genome-wide regulatory programs remain poorly understood. Here we describe DisP-seq (disordered protein precipitation followed by DNA sequencing), an antibody-independent chemical precipitation assay that can simultaneously map endogenous DNA-associated disordered proteins genome-wide through a combination of biotinylated isoxazole precipitation and next-generation sequencing. DisP-seq profiles are composed of thousands of peaks that are associated with diverse chromatin states, are enriched for disordered transcription factors (TFs) and are often arranged in large lineage-specific clusters with high local concentrations of disordered proteins and different combinations of histone modifications linked to regulatory potential. We use DisP-seq to analyze cancer cells and reveal how disordered protein-associated islands enable IDR-dependent mechanisms that control the binding and function of disordered TFs, including oncogene-dependent sequestration of TFs through long-range interactions and the reactivation of differentiation pathways upon loss of oncogenic stimuli in Ewing sarcoma.

DOI: 10.1038/s41587-023-01737-4

Source: https://www.nature.com/articles/s41587-023-01737-4

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex