Muscle fiber type specific activation of the slow myosin heavy chain 2 promoter by a non-canonical E-box.
Muscle fiber type specific activation of the slow myosin heavy chain 2 promoter by a non-canonical E-box.
复制标题
非典型 E-box 对慢肌球蛋白重链 2 启动子的肌纤维类型特异性激活。
DOI：
10.1016/j.bbrc.2015.12.013
复制
发表时间：
2016
影响因子：
3.1
通讯作者：
DiMario,JosephX
中科院分区：
文献类型：
--
作者：
Weimer,Kristina;DiMario,JosephX
在脊椎动物发育的特定时期，不同的机制控制着骨骼肌纤维型基因的表达。在禽类中，胚胎肌肉发生导致初级肌肉纤维的形成在很大程度上是由成肌细胞承诺形成不同类型的纤维所指导的。相反，在胎儿肌肉发生过程中，不同次级纤维类型的发育部分是由神经影响决定的。在初级和次级鸡肌纤维中，慢肌球蛋白重链2(MyHC2)基因的差异表达区分了快肌纤维和快/慢肌纤维。本研究主要研究不同快/慢和快肌细胞系形成的原代肌管中慢速MyHC2基因的转录调控。启动子缺失分析确定了一个86个碱基的离散启动子片段，该片段赋予了快/慢与快成肌细胞来源的初级肌管中纤维类型、谱系特异性基因表达。序列分析和启动子活性分析表明，该片段含有两个功能顺式调控元件。其中一个元件是一个非规范的E-box，电迁移率分析表明两个顺式元件都与E-蛋白E47相互作用。结果表明，慢速MyHC2基因的初级肌纤维型特异性表达受一种新的机制控制，该机制涉及到一个转录复合体，该复合体在一个非规范的E-box上包括E47。
Different mechanisms control skeletal muscle fiber type gene expression at specific times in vertebrate development. Embryonic myogenesis leading to formation of primary muscle fibers in avian species is largely directed by myoblast cell commitment to the formation of diverse fiber types. In contrast, development of different secondary fiber types during fetal myogenesis is partly determined by neural influences. In both primary and secondary chicken muscle fibers, differential expression of the slow myosin heavy chain 2 (MyHC2) gene distinguishes fast from fast/slow muscle fibers. This study focused on the transcriptional regulation of the slow MyHC2 gene in primary myotubes formed from distinct fast/slow and fast myogenic cell lineages. Promoter deletion analyses identified a discrete 86 bp promoter segment that conferred fiber type, lineage-specific gene expression in fast/slow versus fast myoblast derived primary myotubes. Sequence analysis and promoter activity assays determined that this segment contains two functional cis-regulatory elements. One element is a non-canonical E-box, and electromobility shift assays demonstrated that both cis-elements interacted with the E-protein, E47. The results indicate that primary muscle fiber type specific expression of the slow MyHC2 gene is controlled by a novel mechanism involving a transcriptional complex that includes E47 at a non-canonical E-box.