Characterization of the promoter region of the bovine SIX1 gene: Roles of MyoD, PAX7, CREB and MyoG.
Characterization of the promoter region of the bovine SIX1 gene: Roles of MyoD, PAX7, CREB and MyoG.
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DOI：
10.1038/s41598-017-12787-5
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发表时间：
2017-10-03
影响因子：
4.6
通讯作者：
Zan LS
中科院分区：
文献类型：
--
作者：
Wei DW;Ma XY;Zhang S;Hong JY;Gui LS;Mei CG;Guo HF;Wang L;Ning Y;Zan LS
SIX 1基因属于六个同源域转录因子（homeodomain transcription factors，TF）家族，调节细胞外信号调节激酶1/2（extracellular signal-regulated kinase 1/2，ERK 1/2）通路，介导骨骼肌的生长和再生。先前的研究表明SIX 1与身体测量性状（BMTs）正相关。然而，SIX 1的转录调控仍不清楚。在本研究中，我们确定牛SIX 1在胸最长肌中高度表达。为了阐明参与牛SIX 1调控的分子机制，获得了2-kb的5′调控区。序列分析表明，牛SIX 1基因5′侧翼区既没有TATA盒，也没有CCAAT盒。然而，在相对于转录起始位点（TSS）的−235至+658区域预测了CpG岛。电泳迁移率变动分析（EMSA）和染色质免疫沉淀（ChIP）分析结合5′侧翼区的连续缺失构建体、定点突变和siRNA干扰证明MyoD、PAX 7和CREB结合发生在区域−689/−40，并且在牛SIX 1转录中起重要作用。此外，MyoG通过MEF 3基序间接驱动SIX 1转录。总之，这些相互作用表明SIX 1在介导牛骨骼肌生长中的关键功能作用。
The SIX1 gene belongs to the family of six homeodomain transcription factors (TFs), that regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and mediate skeletal muscle growth and regeneration. Previous studies have demonstrated that SIX1 is positively correlated with body measurement traits (BMTs). However, the transcriptional regulation of SIX1 remains unclear. In the present study, we determined that bovine SIX1 was highly expressed in the longissimus thoracis. To elucidate the molecular mechanisms involved in bovine SIX1 regulation, 2-kb of the 5′ regulatory region were obtained. Sequence analysis identified neither a consensus TATA box nor a CCAAT box in the 5′ flanking region of bovine SIX1. However, a CpG island was predicted in the region −235 to +658 relative to the transcriptional start site (TSS). An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay in combination with serial deletion constructs of the 5′ flanking region, site-directed mutation and siRNA interference demonstrated that MyoD, PAX7 and CREB binding occur in region −689/−40 and play important roles in bovine SIX1 transcription. In addition, MyoG drives SIX1 transcription indirectly via the MEF3 motif. Taken together these interactions suggest a key functional role for SIX1 in mediating skeletal muscle growth in cattle.
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