Involvement of CTCF in transcription regulation of EGR1 at early G1 phase as an architecture factor
Involvement of CTCF in transcription regulation of EGR1 at early G1 phase as an architecture factor
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CTCF 作为结构因子参与 G1 早期 EGR1 的转录调控
DOI：
10.1038/s41598-018-36753-x
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发表时间：
2019
影响因子：
4.6
通讯作者：
Nagata Kyosuke
中科院分区：
文献类型：
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作者：
Sekiya Takeshi;Kato Kohsuke;Kawaguchi Atsushi;Nagata Kyosuke
早期生长反应1（EGR 1）是一种转录因子，调节细胞增殖、分化和细胞凋亡等过程。EGR1基因的表达在多种刺激下迅速被诱导，并激活下游参与信号转导的靶基因的表达，在G1期早期转录。然而，EGR1在G1期早期的转录调控尚不清楚。我们发现，在G1期早期，EGFR 1基因的转录需要一种染色质结合蛋白CCCTC结合因子（CTCF）。我们发现CTCF介导位于theEGR1位点的CTCF结合位点之间的高级染色质结构的形成。使用核酸酶死亡Cas9（dCas9）介导的干扰破坏CTCF依赖的高阶染色质结构减少了G1早期的EGFR 1转录。总的来说，我们认为CTCF通过调节更高级的染色质结构组织，在早期G1期对EGR1的时间表达具有功能作用。
Early growth response 1 (EGR1) is a transcription factor and regulates cellular processes such as proliferation, differentiation, and apoptosis. The expression of EGR1 is rapidly induced in response to several stimuli, and it activates the expression of downstream target genes involved in signaling cascades.EGR1gene is also known to be transcribed in early G1 phase. However, the regulation ofEGR1transcription in early G1 phase is not clarified well. Here we found that CCCTC-binding factor (CTCF), a chromatin binding protein, is required to transcribeEGR1gene at the onset of early G1 phase. We found that CTCF mediated the formation of higher-order chromatin structures among CTCF binding sites located in theEGR1locus. Disruption of the CTCF-dependent higher-order chromatin structure using nuclease-dead Cas9 (dCas9)-mediated interference reduced theEGR1transcription in early G1 phase. Collectively, we propose that CTCF has functional roles for the temporal expression ofEGR1in early G1 phase through regulation of higher-order chromatin structure organization.