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Background <p>It is widely recognized that histone deacetylase 11 (HDAC11) plays vital roles in a variety of biological processes including apoptosis, immunity and lipid metabolism in mammals, however, its role in zebrafish remains poorly elucidated. Here, we demonstrated that <i>hdac11</i> knockout increases <i>pdcd6</i> expression via <i>pdcd6</i> + 310k enhancer, then promotes apoptosis in zebrafish cells under cold stress.</p> Methods and results <p>The current work reported that inhibition of Hdac11 promoted apoptosis and up-regulated <i>programmed cell death protein 6</i> (<i>pdcd6</i>) in ZF4 cells under cold stress. ChIP-qPCR showed the enrichment of H3K27ac and Hdac11 at the + 310k region downstream of <i>pdcd6</i>. Dual-luciferase assay confirmed the enhancer activity of <i>pdcd6</i> + 310k region. Chromatin conformation capture (3C) assay showed that <i>pdcd6</i> promoter interacted with + 310k region, and that interaction frequency was enhanced after <i>hdac11</i> knockout. Furthermore, siRNA knockdown of <i>pdcd6</i> rescued the apoptosis induced by Hdac11 inhibition or cold stress in ZF4 cells.</p> Conclusions <p>In summary, Hdac11 targets <i>pdcd6</i> + 310k enhancer to repress <i>pdcd6</i> expression, which then inhibits apoptosis in zebrafish cells.</p>

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Hdac11 inhibits apoptosis in zebrafish cells under cold stress via downregulating pdcd6 through its downstream enhancer

  • 期刊论文

  • 发表日期：

    2025年8月26日

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  • Mingzhi Ma,
  • Juntao Luo,
  • Xin Li,
  • Rui Deng,
  • Hui Jiang,
  • Bingshe Han,
  • Junfang Zhang

摘要

Background

It is widely recognized that histone deacetylase 11 (HDAC11) plays vital roles in a variety of biological processes including apoptosis, immunity and lipid metabolism in mammals, however, its role in zebrafish remains poorly elucidated. Here, we demonstrated that hdac11 knockout increases pdcd6 expression via pdcd6 + 310k enhancer, then promotes apoptosis in zebrafish cells under cold stress.

Methods and results

The current work reported that inhibition of Hdac11 promoted apoptosis and up-regulated programmed cell death protein 6 (pdcd6) in ZF4 cells under cold stress. ChIP-qPCR showed the enrichment of H3K27ac and Hdac11 at the + 310k region downstream of pdcd6. Dual-luciferase assay confirmed the enhancer activity of pdcd6 + 310k region. Chromatin conformation capture (3C) assay showed that pdcd6 promoter interacted with + 310k region, and that interaction frequency was enhanced after hdac11 knockout. Furthermore, siRNA knockdown of pdcd6 rescued the apoptosis induced by Hdac11 inhibition or cold stress in ZF4 cells.

Conclusions

In summary, Hdac11 targets pdcd6 + 310k enhancer to repress pdcd6 expression, which then inhibits apoptosis in zebrafish cells.