N-Myc regulates a widespread euchromatic program in the human genome partially independent of its role as a classical transcription factor.
N-Myc regulates a widespread euchromatic program in the human genome partially independent of its role as a classical transcription factor.
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DOI：
10.1158/0008-5472.can-08-1961
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发表时间：
2008-12-01
期刊：
影响因子：
11.2
通讯作者：
Knoepfler PS
中科院分区：
文献类型：
--
作者：
Cotterman R;Jin VX;Krig SR;Lemen JM;Wey A;Farnham PJ;Knoepfler PS
Myc蛋白长期以来一直被建模为严格作为经典的基因特异性转录因子来操作，然而我们发现N-Myc在人类基因组中在调节包括基因间区域的全局细胞常染色质中具有强大的作用。引人注目的是，90-95%的总基因组常染色质标记组蛋白H3在赖氨酸9处乙酰化和在赖氨酸4处甲基化是N-Myc依赖性的。然而，Myc对转录的调控，甚至是它直接结合的基因的转录，以及维持活性染色质所需的转录，通常都很弱。因此，Myc具有比影响单个基因转录更有效的调节常染色质大结构域的能力。总的来说，Myc对人类基因组中染色质的调控既包括特定的基因，也包括广泛的基因组结构域，这些基因组结构域调用独立于经典转录因子的功能。这些发现支持了Myc染色质功能的新双重模型，对Myc在癌症和干细胞生物学中的作用具有重要意义，包括诱导多能干细胞（iPS）。
Myc proteins have long been modeled to operate strictly as classical gene specific transcription factors, however we find that N-Myc has a robust role in the human genome in regulating global cellular euchromatin including that of intergenic regions. Strikingly, 90–95% of the total genomic euchromatic marks histone H3 acetylated at lysine 9 and methylated at lysine 4 is N-Myc dependent. However, Myc regulation of transcription, even of genes it directly binds and at which it is required for maintenance of active chromatin, is generally weak. Thus, Myc has a much more potent ability to regulate large domains of euchromatin than to influence transcription of individual genes. Overall, Myc regulation of chromatin in the human genome includes both specific genes, but also expansive genomic domains that invoke functions independent of a classical transcription factor. These findings support a new dual model for Myc chromatin function with important implications for the role of Myc in cancer and stem cell biology, including that of induced pluripotent stem (iPS) cells.