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首页> 外文期刊>Molecular and Cellular Biology >Evaluation of Myc E-Box Phylogenetic Footprints in Glycolytic Genes by Chromatin Immunoprecipitation Assays
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Evaluation of Myc E-Box Phylogenetic Footprints in Glycolytic Genes by Chromatin Immunoprecipitation Assays

机译：染色质免疫沉淀法评估糖酵解基因中Myc E-Box系统发生的足迹

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Prediction of gene regulatory sequences using phylogenetic footprinting has advanced considerably but lacks experimental validation. Here, we report whether transcription factor binding sites predicted by dot plotting or web-based Trafac analysis could be validated by chromatin immunoprecipitation assays. MYC overexpression enhances glycolysis without hypoxia and hence may contribute to altered tumor metabolism. Because the full spectrum of glycolytic genes directly regulated by Myc is not known, we chose Myc as a model transcription factor to determine whether it binds target glycolytic genes that have conserved canonical Myc binding sites or E boxes (5′-CACGTG-3′). Conserved canonical E boxes in ENO1, HK2, and LDHA occur in 31- to 111-bp islands with high interspecies sequence identity (>65%). Trafac analysis revealed another region in ENO1 that corresponds to a murine region with a noncanonical E box. Myc bound all these conserved regions well in the human P493-6 B lymphocytes. We also determined whether Myc could bind nonconserved canonical E boxes found in the remaining human glycolytic genes. Myc bound PFKM, but it did not significantly bind GPI, PGK1, and PKM2. Binding to BPGM, PGAM2, and PKLR was not detected. Both GAPD and TPI1 do not have conserved E boxes but are induced and bound by Myc through regions with noncanonical E boxes. Our results indicate that Myc binds well to conserved canonical E boxes, but not nonconserved E boxes. However, the binding of Myc to unpredicted genomic regions with noncanonical E boxes reveals a limitation of phylogenetic footprinting. In aggregate, these observations indicate that Myc is an important regulator of glycolytic genes, suggesting that MYC plays a key role in a switch to glycolytic metabolism during cell proliferation or tumorigenesis.
机译：使用系统发育足迹的基因调控序列的预测已大大提高，但缺乏实验验证。在这里，我们报告是否可以通过染色质免疫沉淀测定法验证通过斑点绘图或基于Web的Trafac分析预测的转录因子结合位点。 MYC 的过度表达增强了糖酵解而没有缺氧，因此可能导致肿瘤代谢的改变。由于尚不清楚由Myc直接调控的糖酵解基因的全谱，因此我们选择Myc作为模型转录因子来确定其是否结合具有保守Myc结合位点或E框的目标糖酵解基因（5'-CACGTG-3'） 。 ENO1 ， HK2 和 LDHA 中的保守正则E盒出现在31至111 bp的岛上，具有较高的种间序列同一性（> 65％ ）。 Trafac分析揭示了 ENO1 中的另一个区域，该区域与带有非规范E框的鼠类区域相对应。 Myc在人P493-6 B淋巴细胞中很好地结合了所有这些保守区域。我们还确定Myc是否可以结合在其余人类糖酵解基因中发现的非保守经典E盒。 Myc绑定了 PFKM ，但没有显着绑定 GPI，PGK1 和 PKM2 。未检测到与 BPGM ， PGAM2 和 PKLR 的绑定。 GAPD 和 TPI1 都没有保守的E盒，但被Myc通过具有非经典E盒的区域诱导和结合。我们的结果表明，Myc与保守的标准E盒结合良好，但对非保守的E盒则没有。但是，Myc与非规范的E框绑定到不可预测的基因组区域揭示了系统发育足迹的局限性。总体而言，这些观察结果表明Myc是糖酵解基因的重要调节剂，表明 MYC 在细胞增殖或肿瘤发生过程中向糖酵解代谢的转换中起关键作用。

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