【Publications】Chromatin structure undergoes global and local reorganization during murine dendritic cell development and activation (Published in PNAS)

August 17 2022

Daisuke Kurotaki

Paper Information

Title:

Chromatin structure undergoes global and local reorganization during murine dendritic cell development and activation (Published in PNAS)

Daisuke Kurotaki, Kenta Kikuchi, Kairong Cui, Wataru Kawase, Keita Saeki, Junpei Fukumoto, Akira Nishiyama, Kisaburo Nagamune, Kiji Zhao, Keiko Ozato, Pedro P. Rocha and Tomohiko Tamura

Proceedings of the National Academy of Sciences of the United States of America  August 15, 2022 119 (34) e2207009119

doi: https://doi.org/10.1073/pnas.2207009119

Abstract:

Dendritic cells (DCs), essential for immune responses, originate from bone marrow hematopoietic stem cells via intermediate progenitors. In eukaryotic nuclei, DNA is packaged into 3D chromatin structures that have been implicated in gene regulation. However, the chromatin structure reorganization dynamics during DC differentiation remain unknown. Here, we analyzed 3D chromatin structures in DCs and their progenitors. In genomic regions at DC-specific genes, the 3D chromatin structures were reorganized upon DC differentiation. The transcription factor IRF8 promoted chromatin structure changes in DC progenitors, leading to DC-specific gene induction. Strikingly, the chromatin structures of infection-inducible genes were preestablished in unstimulated DCs. Our findings advance the understanding of DC biology and basic principles of gene regulation for cell differentiation and host defense.

樹状細胞はウイルスなどの病原体に対する免疫応答に必須の骨髄由来細胞です。IRCMSの黒滝らはマウス生体に由来する樹状細胞と複数段階の骨髄前駆細胞を用い、Hi-C法でクロマチン高次構造の変化を網羅的に解析しました。その結果、樹状細胞に特徴的に発現する遺伝子を含むDNA領域では、樹状細胞前駆細胞の段階で核内コンパートメントと呼ばれるクロマチン高次構造が活性化型に変化し、樹状細胞に分化する段階でトポロジカル関連ドメインと呼ばれる構造が強く形成されることがわかりました。さらにこの核内コンパートメントの活性化型への変化には転写因子IRF8が関与することを明らかにしました。また、感染防御に関与する遺伝子のクロマチン高次構造は感染の前にはすでに準備されており、それによって樹状細胞が病原体に対し素早く反応して必要な遺伝子発現が誘導できることがわかりました。

熊本大学プレスリリース（Japanese)