MYC recruits the TIP60 histone acetyltransferase complex to chromatin

MYC recruits the TIP60 histone acetyltransferase complex to chromatin
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DOI:
10.1038/sj.embor.embor861
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发表时间:
2003-06-01
期刊:
影响因子:
7.7
通讯作者:
Amati, B
Amati, B
中科院分区:
生物学2区
文献类型:
--
作者:
Frank, SR;Parisi, T;Amati, B

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转录因子MYC结合细胞染色质上的特定DNA位点并诱导组蛋白H3和H4的乙酰化。然而,负责这些修饰的组蛋白乙酰转移酶(HATs)尚未被确定。MYC与TRRAP结合,TRRAP是包含HATs GCN5/PCAF或TIP60的不同大分子复合物的一个亚基。尽管MYC与GCN5的关联已被证实,但其与TIP60的相互作用从未被分析过。在这里,我们发现MYC与TIP60结合,并在体内与TIP60复合体的其他四个组分(TRRAP、p400、TIP48和TIP49)一起将其招募到染色质上。酶失活TIP60的过表达延迟了MYC诱导的组蛋白H4的乙酰化,也降低了MYC与染色质结合的水平。因此,TIP60 HAT复合体被招募到myc靶基因上,并可能与其他HAT一起,在响应有丝分裂信号时促进组蛋白乙酰化。
The transcription factor MYC binds specific DNA sites in cellular chromatin and induces the acetylation of histones H3 and H4. However, the histone acetyltransferases (HATs) that are responsible for these modifications have not yet been identified. MYC associates with TRRAP, a subunit of distinct macromolecular complexes that contain the HATs GCN5/PCAF or TIP60. Although the association of MYC with GCN5 has been shown, its interaction with TIP60 has never been analysed. Here, we show that MYC associates with TIP60 and recruits it to chromatin in vivo with four other components of the TIP60 complex: TRRAP, p400, TIP48 and TIP49. Overexpression of enzymatically inactive TIP60 delays the MYC-induced acetylation of histone H4, and also reduces the level of MYC binding to chromatin. Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.