近日，西班牙巴塞罗那科技学院 Thomas Graf、Grégoire Stik、荷兰伊拉斯姆斯大学Ralph Stadhouders等研究人员发现，CTCF对于免疫细胞转分化非必需，但可促进急性炎症反应。这一研究成果于2020年6月8日在线发表在《自然—遗传学》上。

Title: CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response

Author: Grgoire Stik, Enrique Vidal, Mercedes Barrero, Sergi Cuartero, Maria Vila-Casadess, Julen Mendieta-Esteban, Tian V. Tian, Jinmi Choi, Clara Berenguer, Amaya Abad, Beatrice Borsari, Franois le Dily, Patrick Cramer, Marc A. Marti-Renom, Ralph Stadhouders, Thomas Graf

Issue&Volume: 2020-06-08

Abstract: Three-dimensional organization of the genome is important for transcriptional regulation1,2,3,4,5,6,7. In mammals, CTCF and the cohesin complex create submegabase structures with elevated internal chromatin contact frequencies, called topologically associating domains (TADs)8,9,10,11,12. Although TADs can contribute to transcriptional regulation, ablation of TAD organization by disrupting CTCF or the cohesin complex causes modest gene expression changes13,14,15,16. In contrast, CTCF is required for cell cycle regulation17, embryonic development and formation of various adult cell types18. To uncouple the role of CTCF in cell-state transitions and cell proliferation, we studied the effect of CTCF depletion during the conversion of human leukemic B cells into macrophages with minimal cell division. CTCF depletion disrupts TAD organization but not cell transdifferentiation. In contrast, CTCF depletion in induced macrophages impairs the full-blown upregulation of inflammatory genes after exposure to endotoxin. Our results demonstrate that CTCF-dependent genome topology is not strictly required for a functional cell-fate conversion but facilitates a rapid and efficient response to an external stimulus.

DOI: 10.1038/s41588-020-0643-0

Source: https://www.nature.com/articles/s41588-020-0643-0