Translational control of skeletal muscle mass by the transcriptional repressor BCL6. Translational control of skeletal muscle mass by the transcriptional repressor BCL6

Using mRNA-seq and ChIP-seq in muscle tissue, we found that BCL6 controls a broad range of anabolic targets, directly suppressing eukaryotic translation initiation factor 4E-binding protein 1 (Eif4epb1) and myostatin (Mstn) while enhancing insulin-like growth factor 1 (Igf1) and androgen receptor (Ar). Consistent with these gene regulatory effects, skeletal muscle ablation of Bcl6 increased physical association of the translation initiation factor eIF4E with its inhibitor EIF4E-BP1 and ribosomal sequencing in vivo revealed reduced translation efficiency. Overall design: Genome-wide maps of chromatin state, gene expression, and translation efficiency in skeletal muscle in wild-type, control, and Bcl6 knock-out mice.

本研究通过在肌肉组织中开展mRNA测序（mRNA-seq）与染色质免疫共沉淀测序（ChIP-seq），发现BCL6可调控广泛的合成代谢靶标：其能够直接抑制真核翻译起始因子4E结合蛋白1（Eif4epb1）与肌抑素（Mstn），同时增强胰岛素样生长因子1（Igf1）与雄激素受体（Ar）的表达。与上述基因调控效应相一致，骨骼肌中Bcl6的敲除会增加翻译起始因子eIF4E与其抑制剂EIF4E-BP1之间的物理结合，而体内核糖体测序结果显示翻译效率降低。整体实验设计：针对野生型、对照组与Bcl6敲除小鼠的骨骼肌，开展全基因组范围的染色质状态、基因表达及翻译效率图谱分析。