Scholarlink

<p>Circadian disruption and metabolic stress are implicated in Parkinson’s disease (PD), but the epigenetic mechanisms linking nutrient fluctuations to circadian regulation remain poorly understood. Here, we combined genome-wide 5-hydroxymethylcytosine (5hmC) profiling, CRISPR-based genetic perturbations, and circadian models to investigate how glucose availability shapes epigenetic dynamics and circadian transcription. We found that low glucose activates AMP-activated protein kinase (AMPK), upregulating TET2 transcription and increasing global 5hmC remodeling. These effects are reversible upon glucose restoration and are abolished by AMPK deficiency, establishing AMPK as a key mediator of metabolic control over TET2. Notably, <i>Tet2</i> exhibits intrinsic circadian rhythmicity and is temporally coupled with clock-associated gene expression. Disruption of TET2 impairs glucose-responsive 5hmC dynamics and alters circadian transcriptional outputs. Together, our findings define a glucose-responsive AMPK–TET2–5hmC axis that links metabolic state to epigenetic and circadian regulation. This work provides a mechanistic framework for understanding how metabolic dysfunction may contribute to circadian abnormalities in Parkinson’s disease.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Glucose-responsive AMPK-TET2-5hmc oscillation links metabolic stress to circadian transcription and Parkinson’s disease relevance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月23日

查看全文
  • Liuxi Chu,
  • Sisi Wang,
  • Linlin Wang,
  • Feiyu Ding,
  • Wenyuan Wang,
  • Jiajie Mei,
  • Yuqing Li,
  • Wenjie Hu,
  • Ruohan Tong,
  • Chenyu Zhu,
  • Chen Gao,
  • Wenjia Wang,
  • Shui Tian,
  • Jing Cheng,
  • Yalin Zhang

摘要

Circadian disruption and metabolic stress are implicated in Parkinson’s disease (PD), but the epigenetic mechanisms linking nutrient fluctuations to circadian regulation remain poorly understood. Here, we combined genome-wide 5-hydroxymethylcytosine (5hmC) profiling, CRISPR-based genetic perturbations, and circadian models to investigate how glucose availability shapes epigenetic dynamics and circadian transcription. We found that low glucose activates AMP-activated protein kinase (AMPK), upregulating TET2 transcription and increasing global 5hmC remodeling. These effects are reversible upon glucose restoration and are abolished by AMPK deficiency, establishing AMPK as a key mediator of metabolic control over TET2. Notably, Tet2 exhibits intrinsic circadian rhythmicity and is temporally coupled with clock-associated gene expression. Disruption of TET2 impairs glucose-responsive 5hmC dynamics and alters circadian transcriptional outputs. Together, our findings define a glucose-responsive AMPK–TET2–5hmC axis that links metabolic state to epigenetic and circadian regulation. This work provides a mechanistic framework for understanding how metabolic dysfunction may contribute to circadian abnormalities in Parkinson’s disease.