基因调控网络的构建将MYC鉴定为SWI / SNF复合体的转录调控因子。,Scientific Reports

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基因调控网络的构建将MYC鉴定为SWI / SNF复合体的转录调控因子。
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-13 , DOI: 10.1038/s41598-019-56844-7
Srimari Srikanth ₁ , Srimathy Ramachandran ₁ , Suma Mohan S ₁

Affiliation

核小体在SWI / SNF重塑复合体家族介导的基因调控元件上的精确定位对于基因的转录调控非常重要。广泛的基因受SWI / SNF的正调控或负调控。在高级真核生物中，发现约有三十个基因编码SWI / SNF亚基。SWI / SNF亚基的基因调控网络的构建将MYC鉴定为许多SWI / SNF亚基基因的通用调控因子。进行了荟萃分析研究，以调查MYC对SWI / SNF重塑复合物的调控。亚基信息和亚基基因的启动子序列被用来发现典型的E-box基序及其变体。对SWI / SNF亚基位点的小鼠和人类ChIP-Seq的详细分析表明，存在与E-box重叠的MYC结合峰。wt与MYC干扰的MEF的共表达相关性和差异表达分析表明，某些SWI / SNF亚基的MYC依赖性调节。分析的扩展是在MYC熟练和MYC缺乏的胚胎成纤维细胞系TGR1和HO15，以及在MYC扩增的一种癌症类型，髓母细胞瘤中进行的。MYC和SWI / SNF之间的转录调控反馈回路可能是导致MYC依赖性癌症侵袭性的主要因素。分析的扩展是在MYC熟练和MYC缺乏的胚胎成纤维细胞系TGR1和HO15，以及在MYC扩增的一种癌症类型，髓母细胞瘤中进行的。MYC和SWI / SNF之间的转录调控反馈回路可能是导致MYC依赖性癌症侵袭性的主要因素。分析的扩展是在MYC熟练和MYC缺乏的胚胎成纤维细胞系TGR1和HO15，以及在MYC扩增的一种癌症类型，髓母细胞瘤中进行的。MYC和SWI / SNF之间的转录调控反馈回路可能是导致MYC依赖性癌症侵袭性的主要因素。

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Construction of the gene regulatory network identifies MYC as a transcriptional regulator of SWI/SNF complex.

Precise positioning of nucleosomes at the gene regulatory elements mediated by the SWI/SNF family of remodelling complex is important for the transcriptional regulation of genes. A wide set of genes are either positively or negatively regulated by SWI/SNF. In higher eukaryotes, around thirty genes were found to code for SWI/SNF subunits. The construction of a gene regulatory network of SWI/SNF subunits identifies MYC as a common regulator for many of the SWI/SNF subunit genes. A meta-analysis study was conducted to investigate the MYC dependent regulation of SWI/SNF remodelling complex. Subunit information and the promoter sequences of the subunit genes were used to find the canonical E-box motif and its variants. Detailed analysis of mouse and human ChIP-Seq at the SWI/SNF subunit loci indicates the presence of MYC binding peaks overlapping with E-boxes. The co-expression correlation and the differential expression analysis of wt vs. MYC perturbed MEFs indicate the MYC dependent regulation of some of the SWI/SNF subunits. The extension of the analysis was done on MYC proficient and MYC deficient embryonic fibroblast cell lines, TGR1 and HO15, and in one of the MYC amplified cancer types, Medulloblastoma. A transcriptional regulatory feedback loop between MYC and SWI/SNF could be a major factor contributing to the aggressiveness of MYC dependent cancers.

更新日期：2020-01-13

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