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Regulation of IL12B Expression in Human Macrophages by TALEN-mediated Epigenome Editing

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An Erratum to this article was published on 01 December 2020

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Summary

Although the exact etiology of inflammatory bowel disease (IBD) remains unclear, exaggerated immune response in genetically predisposed individuals has been reported. Th1 and Th17 cells mediate IBD development. Macrophages produce IL-12 and IL-23 that share p40 subunit encoded by IL12B gene as heteromer partner to drive Th1 and Th17 differentiation. The available animal and human data strongly support the pathogenic role of IL-12/IL-23 in IBD development and suggest that blocking p40 might be the potential strategy for IBD treatment. Furthermore, aberrant alteration of some cytokines expression via epigenetic mechanisms is involved in pathogenesis of IBD. In this study, we analyzed core promoter region of IL12B gene and investigated whether IL12B expression could be regulated through targeted epigenetic modification with gene editing technology. Transcription activator-like effectors (TALEs) are widely used in the field of genome editing and can specifically target DNA sequence in the host genome. We synthesized the TALE DNA-binding domains that target the promoter of human IL12B gene and fused it with the functional catalytic domains of epigenetic enzymes. Transient expression of these engineered enzymes demonstrated that the TALE-DNMT3A targeted the selected IL12B promoter region, induced loci-specific DNA methylation, and down-regulated IL-12B expression in various human cell lines. Collectively, our data suggested that epigenetic editing of IL12B through methylating DNA on its promoter might be developed as a potential therapeutic strategy for IBD treatment.

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Change history

  • 11 January 2021

    Prof. Mei YE works in the Department of Gastroenterology, Zhongnan Hospital, Wuhan University, and Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, as shown above. Her affiliation was incorrectly indicated in the article.

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Authors and Affiliations

  1. Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

    Meng Chen, Hua Zhu, Yu-juan Mao, Nan Cao, Ya-li Yu & Qiu Zhao

  2. Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, 430071, China

    Meng Chen, Hua Zhu, Yu-juan Mao, Nan Cao, Ya-li Yu & Qiu Zhao

  3. College of Life Sciences, Wuhan University, Wuhan, 430072, China

    Lian-yun Li, Min Wu & Mei Ye

Authors
  1. Meng Chen
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  2. Hua Zhu
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  3. Yu-juan Mao
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  4. Nan Cao
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  5. Ya-li Yu
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  6. Lian-yun Li
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  7. Qiu Zhao
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  8. Min Wu
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  9. Mei Ye
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Correspondence to Mei Ye.

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The study was supported by the National Natural Science Foundation of China (No. 81270468).

Conflict of Interest Statement

The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.

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Chen, M., Zhu, H., Mao, Yj. et al. Regulation of IL12B Expression in Human Macrophages by TALEN-mediated Epigenome Editing. CURR MED SCI 40, 900–909 (2020). https://doi.org/10.1007/s11596-020-2249-2

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  • DOI: https://doi.org/10.1007/s11596-020-2249-2

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