A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells
A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells
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DOI：
10.1073/pnas.1332764100
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发表时间：
2003-07-08
影响因子：
11.1
通讯作者：
Ren, B
中科院分区：
文献类型：
--
作者：
Li, ZR;Van Calcar, S;Ren, B
c-Myc的过表达是人类癌症中最常见的改变之一，但目前尚不清楚这种转录因子如何促进恶性转化。为了了解c-Myc功能的分子靶点，我们使用了一种无偏倚的全基因组定位分析方法来检测伯基特淋巴瘤细胞中c-Myc的基因组结合位点。我们发现c-Myc和它的异二聚体伙伴Max占据了这些癌细胞中测试的基因启动子的150 %。c-Myc和Max的DNA结合与整个基因组的基因表达广泛相关，这是一般转录因子的标志属性。在这些细胞中，c-Myc/Max异源二聚体复合物也与转录因子IID共定位，进一步支持过表达的c-Myc在全球基因调控中的普遍作用。此外，在多种组织和细胞系中，大多数c-Myc靶基因的转录表现出与c-Myc mRNA水平相关的变化，支持c-Myc调节它们的结论。综上所述，这些结果表明c-Myc过表达在某些癌细胞的整体转录调节中具有普遍作用，并指出了c-Myc在恶性转化中的功能的分子机制。
Overexpression of c-Myc is one of the most common alterations in human cancers, yet it is not clear how this transcription factor acts to promote malignant transformation. To understand the molecular targets of c-Myc function, we have used an unbiased genome-wide location-analysis approach to examine the genomic binding sites of c-Myc in Burkitt's lymphoma cells. We find that c-Myc together with its heterodimeric partner, Max, occupy >15% of gene promoters tested in these cancer cells. The DNA binding of c-Myc and Max correlates extensively with gene expression throughout the genome, a hallmark attribute of general transcription factors. The c-Myc/Max heterodimer complexes also colocalize with transcription factor IID in these cells, further supporting a general role for overexpressed c-Myc in global gene regulation. In addition, transcription of a majority of c-Myc target genes exhibits changes correlated with levels of c-myc mRNA in a diverse set of tissues and cell lines, supporting the conclusion that c-Myc regulates them. Taken together, these results suggest a general role for overexpressed c-Myc in global transcriptional regulation in some cancer cells and point toward molecular mechanisms for c-Myc function in malignant transformation.