Scholarlink

<p>Skeletal muscle is crucial for glucose regulation and amino acid storage, significantly influencing overall metabolic balance. Its function is tightly regulated by complex mechanisms, with histone acetylation as a key epigenetic control point. Our previous work identified eIF6 as a key regulator of muscle energy homeostasis and demonstrated its role in modulating histone acetylation in the liver. However, whether similar epigenetic mechanisms underpin eIF6’s effects in muscle remains undetermined. To investigate this, we measured H3K9 acetylation levels and HDAC activity both in vivo, using eIF6<sup>+/–</sup> mice, and in vitro, following eIF6 depletion. Our findings demonstrate that eIF6 downregulation in C2C12 myoblasts drives an increase in histone acetylation, a pattern also evident in heterozygous eIF6 primary satellite cells, both in their undifferentiated state and following differentiation. In vivo, eIF6<sup>+/−</sup> mice show pronounced histone hyperacetylation, especially in younger animals, which correlates with a specific decrease in class II HDACs, particularly HDAC4 and HDAC5. This trend is further supported by in vitro data and findings from Drosophila eIF6<sup>+/−</sup> mutants, both of which exhibit decreased HDAC activity. Importantly, the reduction in HDAC4 and HDAC5 activity appears to result from decreased protein levels, driven by eIF6-dependent translational regulation of their mRNAs. All together, these findings establish a link between mRNA translation and histone acetylation in muscle, underpinning translational control as a master regulator of histone acetylation.</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

eIF6 links histone acetylation with translational control of HDAC in skeletal muscle

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月29日

查看全文
  • Alessandra Scagliola,
  • Annarita Miluzio,
  • Ivan Ferrari,
  • Daniel Brina,
  • Sara Ricciardi,
  • Stefano Biffo

摘要

Skeletal muscle is crucial for glucose regulation and amino acid storage, significantly influencing overall metabolic balance. Its function is tightly regulated by complex mechanisms, with histone acetylation as a key epigenetic control point. Our previous work identified eIF6 as a key regulator of muscle energy homeostasis and demonstrated its role in modulating histone acetylation in the liver. However, whether similar epigenetic mechanisms underpin eIF6’s effects in muscle remains undetermined. To investigate this, we measured H3K9 acetylation levels and HDAC activity both in vivo, using eIF6+/– mice, and in vitro, following eIF6 depletion. Our findings demonstrate that eIF6 downregulation in C2C12 myoblasts drives an increase in histone acetylation, a pattern also evident in heterozygous eIF6 primary satellite cells, both in their undifferentiated state and following differentiation. In vivo, eIF6+/− mice show pronounced histone hyperacetylation, especially in younger animals, which correlates with a specific decrease in class II HDACs, particularly HDAC4 and HDAC5. This trend is further supported by in vitro data and findings from Drosophila eIF6+/− mutants, both of which exhibit decreased HDAC activity. Importantly, the reduction in HDAC4 and HDAC5 activity appears to result from decreased protein levels, driven by eIF6-dependent translational regulation of their mRNAs. All together, these findings establish a link between mRNA translation and histone acetylation in muscle, underpinning translational control as a master regulator of histone acetylation.