ZFP281 Recruits MYC to Active Promoters in Regulating Transcriptional Initiation and Elongation

ZFP281 Recruits MYC to Active Promoters in Regulating Transcriptional Initiation and Elongation
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ZFP281 将 MYC 募集到主动启动子中以调节转录起始和延伸

DOI:
10.1128/mcb.00329-19
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发表时间:
2019-12-01
影响因子:
5.3
通讯作者:
Lin, Chengqi
Lin, Chengqi
中科院分区:
生物学2区
文献类型:
--
作者:
Luo, Zhuojuan;Liu, Xiaoxu;Lin, Chengqi

文献摘要

被引文献

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MYC转录因子在转录调控中的作用已被广泛研究。然而,MYC向染色质募集的一般机制尚不清楚。在这里,我们发现Kruppel样转录因子ZFP281在小鼠胚胎干细胞中招募MYC为活性启动子起着重要作用。在基因组水平上,ZFP 281与MYC广泛相关,ZFP 281的缺失显著降低了ZFP 281和MYC共结合基因上的MYC和RNA聚合酶II的水平。特别是,我们发现Lin28a癌基因和pri-let-7转录的调控需要重新启动。因此,我们的结果表明,ZFP 281在将MYC招募到染色质以及将ZFP 281和MYC/Lin28a/let-7环整合到多电平电路中起着重要作用。
The roles of the MYC transcription factor in transcriptional regulation have been studied intensively. However, the general mechanism underlying the recruitment of MYC to chromatin is less clear. Here, we found that the Kruppel-like transcription factor ZFP281 plays important roles in recruiting MYC to active promoters in mouse embryonic stem cells. At the genome scale, ZFP281 is broadly associated with MYC, and the depletion of ZFP281 significantly reduces the levels of MYC and RNA polymerase II at the ZFP281- and MYC-cobound genes. Specially, we found that recruitment is required for the regulation of the Lin28a oncogene and pri-let-7 transcription. Our results therefore suggest a major role of ZFP281 in recruiting MYC to chromatin and the integration of ZFP281 and the MYC/LIN28A/Let-7 loop into a multilevel circuit.