2. Academic Validation
  3. The regulatory effect of acetylation of HMGN2 and H3K27 on pyocyanin-induced autophagy in macrophages by affecting Ulk1 transcription

The regulatory effect of acetylation of HMGN2 and H3K27 on pyocyanin-induced autophagy in macrophages by affecting Ulk1 transcription

  • J Cell Mol Med. 2021 Aug;25(15):7524-7537. doi: 10.1111/jcmm.16788.
Yu Du 1 2,  Hongjun Guo 3,  Lijuan Guo 1,  Junming Miao 1,  Hongyu Ren 1,  Keyun Liu 4,  Laibin Ren 1,  Jinchen He 1,  Xiaoying Wang 1,  Junli Chen 1,  Jingyu Li 1,  Yi Wang 1,  Ji Wang 5,  Ning Huang 1
Affiliations

Affiliations

  • 1 Department of Pathophysiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
  • 2 Department of Anesthesiology, Nanchong Central Hospital, Second Clinical Medical Institution, North Sichuan Medical College, Nanchong, China.
  • 3 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 4 Department of Physiology, School of Medicine, Hubei University for Nationalities, Enshi, China.
  • 5 Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
PMID: 34278675 DOI: 10.1111/jcmm.16788
Abstract

Pyocyanin (PYO) is a major virulence factor secreted by Pseudomonas aeruginosa, and Autophagy is a crucial homeostatic mechanism for the interaction between the pathogens and the host. It remains unknown whether PYO leads to Autophagy in macrophages by regulating histone acetylation. The high mobility group nucleosomal binding domain 2 (HMGN2) has been reported to regulate the PYO-induced Autophagy and oxidative stress in the epithelial cells; however, the underlying molecular mechanism has not been fully elucidated. In this study, PYO was found to induce Autophagy in macrophages, and the mechanism might be correlated with the up-regulation of HMGN2 acetylation (HMGN2ac) and the down-regulation of H3K27 acetylation (H3K27ac) by modulation of the activities of acetyltransferases and deacetylases. Moreover, we further demonstrated that the up-regulated HMGN2ac enhances its recruitment to the ULK1 promoter, while the down-regulation of H3K27ac reduces its recruitment to the ULK1 promoter, thereby promoting or inhibiting the transcription of ULK1. In conclusion, HMGN2ac and H3K27ac play regulatory roles in the PYO-induced Autophagy in macrophages.

Keywords

H3K27; HMGN2; acetylation; autophagy; macrophages; pyocyanin.

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