小柯机器人

荷兰鹿特丹伊拉斯姆斯大学医学中心Joost Gribnau小组取得一项新突破。他们的最新研究对增强子活性和转录组史进行了分析。该项研究成果发表在2023年2月23日出版的《自然—生物技术》上。

在本项研究中，研究人员使用一种可诱导的DCM-RNA聚合酶亚基b融合蛋白对S期细胞的活性基因和增强子进行细菌甲基化标记但不影响基因转录。这种DCM-RNA聚合酶融合蛋白能够标记转录基因和活性增强子，并在发育或分化的后期阶段进行检测。研究人员利用这种DCM-时光机（DCM-TM）技术来研究肠道稳态，揭示了肠细胞分化过程中增强子和附近基因的快速协同激活。

该研究对肠道干细胞（ISC）分化的吸收-分泌谱系提供了新的见解，并表明ISC保留了维持ISC特性和描绘分化相关基因表达所需的独特染色质景观。DCM-TM在跟踪细胞状态方面具有广泛的适用性，为细胞状态变化背后的调控网络提供了新的见解。

据了解，基因调控网络调控了发育和疾病发生过程中的细胞状态变化，但难以实时跟踪其动态。

 附：英文原文

Title: Retrospective analysis of enhancer activity and transcriptome history

Author: Boers, Ruben, Boers, Joachim, Tan, Beatrice, van Leeuwen, Marieke E., Wassenaar, Evelyne, Sanchez, Erlantz Gonzalez, Sleddens, Esther, Tenhagen, Yasha, Mulugeta, Eskeatnaf, Laven, Joop, Creyghton, Menno, Baarends, Willy, van IJcken, Wilfred F. J., Gribnau, Joost

Issue&Volume: 2023-02-23

Abstract: Cell state changes in development and disease are controlled by gene regulatory networks, the dynamics of which are difficult to track in real time. In this study, we used an inducible DCM–RNA polymerase subunit b fusion protein which labels active genes and enhancers with a bacterial methylation mark that does not affect gene transcription and is propagated in S-phase. This DCM–RNA polymerase fusion protein enables transcribed genes and active enhancers to be tagged and then examined at later stages of development or differentiation. We apply this DCM-time machine (DCM-TM) technology to study intestinal homeostasis, revealing rapid and coordinated activation of enhancers and nearby genes during enterocyte differentiation. We provide new insights in absorptive–secretory lineage decision-making in intestinal stem cell (ISC) differentiation and show that ISCs retain a unique chromatin landscape required to maintain ISC identity and delineate future expression of differentiation-associated genes. DCM-TM has wide applicability in tracking cell states, providing new insights in the regulatory networks underlying cell state changes.

DOI: 10.1038/s41587-023-01683-1

Source: https://www.nature.com/articles/s41587-023-01683-1

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