CTCF controls three-dimensional enhancer network underlying the inflammatory response of bone marrow-derived dendritic cells

• Published in: Nature communications Vol. 14; no. 1; p. 1277
• Main Authors: Yang, Bobae, Kim, Sueun, Jung, Woong-Jae, Kim, Kyungwoo, Kim, Sugyung, Kim, Yong-Jin, Kim, Tae-Gyun, Lee, Eun-Chong, Joo, Jung-Sik, Park, Chae Gyu, Oh, Sumin, Yoo, Kyung Hyun, Kim, Hyoung-Pyo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-03-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 45/15; 49/23; 49/91; 631/250/2502/2170; 631/250/2504/133; 631/250/256; 631/337/100/102; 96/31; Adaptive immunity; Antigen-presenting cells; Antigens; Bone Marrow; CCCTC-Binding Factor; Cell activation; Cell differentiation; Chromatin; Dendritic Cells; Dendritic structure; Depletion; Differentiation (biology); Gene expression; Gene regulation; Genomes; Granulocyte-macrophage colony-stimulating factor; Helper cells; Histones; Humanities and Social Sciences; Inflammation; Inflammatory response; Janus kinase 2; Kinases; Lymphocytes T; multidisciplinary; NF-kappa B; NF-κB protein; Regulatory Sequences, Nucleic Acid; Science; Science (multidisciplinary); Stat5 protein; Transcription factors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-36948-5

Dendritic cells are antigen-presenting cells orchestrating innate and adaptive immunity. The crucial role of transcription factors and histone modifications in the transcriptional regulation of dendritic cells has been extensively studied. However, it is not been well understood whether and how three-dimensional chromatin folding controls gene expression in dendritic cells. Here we demonstrate that activation of bone marrow-derived dendritic cells induces extensive reprogramming of chromatin looping as well as enhancer activity, both of which are implicated in the dynamic changes in gene expression. Interestingly, depletion of CTCF attenuates GM-CSF-mediated JAK2/STAT5 signaling, resulting in defective NF-κB activation. Moreover, CTCF is necessary for establishing NF-κB-dependent chromatin interactions and maximal expression of pro-inflammatory cytokines, which prime Th1 and Th17 cell differentiation. Collectively, our study provides mechanistic insights into how three-dimensional enhancer networks control gene expression during bone marrow-derived dendritic cells activation, and offers an integrative view of the complex activities of CTCF in the inflammatory response of bone marrow-derived dendritic cells.
The role of 3D genome organization is not well understood in the transcriptional regulation of dendritic cells. Here the authors show that activation of dendritic cells in vitro induces dynamic reprogramming of the chromatin looping and enhancer activity linked to changes in gene expression and implicates a role for the chromatin architecture protein CTCF in the inflammatory response of dendritic cells.