Acetylation of PAX7 Controls Muscle Stem Cell Self-Renewal and Differentiation Potential

It has been suggested that muscle stem cell function is regulated by Acetyl-CoA and NAD+ availability, but the mechanisms remain unclear. We identified two acetylation sites on PAX7 that positively regulate its transcriptional activity. Lack of PAX7 acetylation reduces DNA binding, specifically to the homeobox motif. The acetyltransferase MYST1 stimulated by Acetyl-CoA, and the deacetylase SIRT2 stimulated by NAD+, were identified as direct regulators of PAX7 acetylation and asymmetric division in muscle stem cells. Abolishing PAX7 acetylation in mice using CRISPR/Cas9 mutagenesis led to an expansion of the satellite stem cell pool, reduced numbers of asymmetric stem cell divisions, and increased numbers of oxidative IIA myofibers. Gene expression analysis confirmed that lack of PAX7 acetylation preferentially affects the expression of target genes regulated by homeodomain binding motifs. Thus, PAX7 acetylation status regulates muscle stem cell function and differentiation potential to facilitate metabolic adaptation of muscle tissue.已有研究提示，乙酰辅酶A（Acetyl-CoA）与烟酰胺腺嘌呤二核苷酸（NAD+）的可获得性可调控肌肉干细胞功能，但其具体分子机制仍不明确。本研究鉴定出PAX7蛋白上的两个乙酰化位点，二者可正向调控其转录活性。PAX7乙酰化缺失会降低其DNA结合能力，尤其是针对同源盒基序的结合活性。研究发现，受乙酰辅酶A激活的乙酰转移酶MYST1，以及受烟酰胺腺嘌呤二核苷酸激活的去乙酰化酶SIRT2，是肌肉干细胞中PAX7乙酰化与干细胞不对称分裂的直接调控因子。通过CRISPR/Cas9诱变技术消除小鼠体内PAX7的乙酰化修饰后，卫星干细胞池出现扩增，干细胞不对称分裂的数量减少，氧化型IIA肌纤维的数量有所增加。基因表达分析证实，PAX7乙酰化缺失会优先影响受同源结构域结合基序调控的靶基因的表达。综上，PAX7的乙酰化状态可调控肌肉干细胞功能与分化潜能，进而促进肌肉组织的代谢适应。

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背景概述

该数据集名为'Acetylation of PAX7 Controls Muscle Stem Cell Self-Renewal and Differentiation Potential'，主要研究PAX7蛋白乙酰化对肌肉干细胞功能的调控机制。数据集包含6个小鼠卫星细胞的RNA-Seq样本，使用Illumina NextSeq 500平台生成转录组数据，旨在探索乙酰化如何影响干细胞自我更新和分化，涉及MYST1和SIRT2酶的作用。数据以fastq.gz格式提供，总大小约30.03 GB，适用于基因表达分析。