Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation.
Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation.
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细胞类型的独立MYC靶基因揭示了与生物量积累有关的原始特征。
DOI：
10.1371/journal.pone.0026057
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Zeller KI
中科院分区：
文献类型：
--
作者：
Ji H;Wu G;Zhan X;Nolan A;Koh C;De Marzo A;Doan HM;Fan J;Cheadle C;Fallahi M;Cleveland JL;Dang CV;Zeller KI
尽管我们对人类癌症中的遗传改变有了更丰富的了解，但独立于背景的关键致癌转录因子的功能尚未完全阐明。产生Myc转录因子的MYC癌基因在人类癌症中经常改变，并且是许多癌症的主要调控中心。在这方面，我们试图解开Myc功能的原始签名，通过使用高通量基因组方法来识别细胞类型独立的核心Myc靶基因签名。使用携带可诱导MYC的人类B淋巴瘤细胞模型，我们通过染色质免疫沉淀（ChIP）、全局核运行试验和mRNA水平的变化鉴定了一组严格的直接Myc靶基因。我们还鉴定了人胚胎干细胞（ESC）中的直接Myc靶点。我们进一步证明了Myc核心签名（MCS）靶基因集在小鼠和人类ESC以及其他四种人类癌细胞类型中是共享的。值得注意的是，MCS的表达与MYC表达在8,129个微阵列样品中以细胞类型独立的方式相关，其中包括312种细胞和组织类型。此外，与癌前或正常B淋巴细胞相比，Eμ-Myc转基因小鼠淋巴瘤细胞中MCS的表达在体内升高。MCS在人B细胞淋巴瘤、急性白血病、肺癌或尤文肉瘤中的表达与MYC表达具有最高的相关性。该基因标记的注释揭示了Myc在RNA加工、核糖体生物发生和生物量积累中的原始功能，作为其在癌症和干细胞中的关键作用。
The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP), global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs). We further document that a Myc core signature (MCS) set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
4.4
作者：
Brown SJ;Cole MD;Erives AJ
通讯作者：
Erives AJ
影响因子：
46.9
作者：
Ji, Hongkai;Jiang, Hui;Ma, Wenxiu;Johnson, David S.;Myers, Richard M.;Wong, Wing H.
通讯作者：
Wong, Wing H.
影响因子：
14.9
作者：
Greasley, PJ;Bonnard, C;Amati, B
通讯作者：
Amati, B
影响因子：
64.8
作者：
Barna, Maria;Pusic, Aya;Zollo, Ornella;Costa, Maria;Kondrashov, Nadya;Rego, Eduardo;Rao, Pulivarthi H.;Ruggero, Davide
通讯作者：
Ruggero, Davide