Epigenetic regulation of HDAC2 on TBC protein family members of neutrophils in patients with ischemic stroke

doi:10.3969/j.issn.1006-7795.2023.01.010

Abstract

Abstract: Objective To study the molecular mechanism that mediating neutrophil degranulation and phagocytosis after acute ischemic stroke(AIS) and the epigenetic regulatory mechanism of histone deacetylase 2 (HDAC2). Methods Three 60－80 years old male patients from the Department of Emergency, Xuanwu Hospital, Capital Medical University who did not receive thrombolysis or endovascular treatment within 6 h after anterior circulation ischemia onset and three healthy gender and age-matched controls were included in this study. The peripheral blood neutrophils was isolated with density gradient centrifugation method, and the transcriptome difference between AIS patients and healthy controls was analyzed with RNA sequencing (RNA-seq). In addition, HDAC2 binding genes in neutrophils were analyzed with chromatin immunoprecipitation high-throughput sequencing (ChIP-seq). Results (1) RNA-seq results indicated that compared with the healthy control group, the transcription level of 13 TBC1D family molecules changed significantly after AIS, among which TBC protein family members TBC1D10A, TBC1D31, and TBC1D5 were significantly down-regulated, and TBC1D10B, TBC1D10C, TBC1D17, TBC1D2, TBC1D22A, TBC1D26, TBC1D29, TBC1D3H, TBC1D8, and TBC1D9B were significantly up-regulated. (2) ChIP-seq analysis indicated that HDAC2 binding genes of TBC1D family in AIS patients were differentially expressed. Methylation analysis of HDAC2 binding promoters showed that these TBC1D family molecules were modified by hypermethylation and moderate methylation, which were regulated by acetylation and methylation modification. Conclusion This study showed that TBC1D family molecules may be potential targets for regulating neutrophil degranulation and phagocytosis after ischemic stroke, and HDAC2 may have extensive binding sites in the genome of this family.

Key words: ischemic stroke, neutrophil, histone deacetylase 2(HDAC2), TBC1D, degranulation, phagocytosis

CLC Number:

R743.3

Li Xue, Fan Junfen, Wang Rongliang, Ma Qingfeng, Luo Yumin, Zhao Haiping. Epigenetic regulation of HDAC2 on TBC protein family members of neutrophils in patients with ischemic stroke[J]. Journal of Capital Medical University, 2023, 44(1): 62-71.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2023.01.010

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2023/V44/I1/62

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