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

Bobae Yang, Sueun Kim, Woong-Jae Jung, Kyungwoo Kim, Sugyung Kim, Yong-Jin Kim, Tae-Gyun Kim, Eun-Chong Lee, Jung-Sik Joo, Chae Gyu Park, Sumin Oh, Kyung Hyun Yoo and Hyoung-Pyo Kim ()
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Bobae Yang: Yonsei University College of Medicine
Sueun Kim: Yonsei University College of Medicine
Woong-Jae Jung: Yonsei University College of Medicine
Kyungwoo Kim: Yonsei University College of Medicine
Sugyung Kim: Yonsei University College of Medicine
Yong-Jin Kim: Yonsei University College of Medicine
Tae-Gyun Kim: Yonsei University College of Medicine
Eun-Chong Lee: Yonsei University College of Medicine
Jung-Sik Joo: Yonsei University College of Medicine
Chae Gyu Park: Yonsei University College of Medicine
Sumin Oh: Sookmyung Women’s University
Kyung Hyun Yoo: Sookmyung Women’s University
Hyoung-Pyo Kim: Yonsei University College of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-36948-5

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