Taming of the beast: shaping Myc-dependent amplification.

Taming of the beast: shaping Myc-dependent amplification.
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DOI:
10.1016/j.tcb.2014.10.006
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发表时间:
2015-04
影响因子:
19
通讯作者:
Levens, David L.
Levens, David L.
中科院分区:
生物学1区
文献类型:
--
作者:
Wolf, Elmar;Lin, Charles Y.;Eilers, Martin;Levens, David L.
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Myc 失调是一种标志性的致癌事件,其中转录因子的过度表达会产生多种致瘤表型。 Myc 放松管制的复杂后果混淆了对其功能的清晰机械解释。最近实验观察的综合提供了对 Myc 直接转录功能的共识——当过度表达时,Myc 广泛参与细胞已建立的常染色质顺式调节景观,在该景观中,该因子通常会放大转录。 Myc 与靶基因的结合水平和转录输出受到其他调节因子(包括 Miz1)的差异调节。针对 Myc 致癌活性需要了解扩增是否会促进肿瘤发生以及适应致癌 Myc 的肿瘤中扩增的后果。
Myc deregulation is a hallmark oncogenic event where overexpression of the transcription factor gives rise to numerous tumorigenic phenotypes. The complex consequences of Myc deregulation have obfuscated clear mechanistic interpretations of its function. A synthesis of recent experimental observations offers a consensus on Myc’s direct transcriptional function — when overexpressed, Myc broadly engages the cell’s established euchromatic cis-regulatory landscape where the factor generally amplifies transcription. The level of Myc binding at target genes and the transcriptional output are differentially modulated by additional regulators, including Miz1. Targeting Myc oncogenic activity will require an understanding of whether amplification promotes tumorigenesis and the consequences of amplification in tumors adapted to oncogenic Myc.
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