Abstract
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. EGR1 gene is also known to be transcribed in early G1 phase. However, the regulation of EGR1 transcription in early G1 phase is not clarified well. Here we found that CCCTC-binding factor (CTCF), a chromatin binding protein, is required to transcribe EGR1 gene 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 the EGR1 locus. Disruption of the CTCF-dependent higher-order chromatin structure using nuclease-dead Cas9 (dCas9)-mediated interference reduced the EGR1 transcription in early G1 phase. Collectively, we propose that CTCF has functional roles for the temporal expression of EGR1 in early G1 phase through regulation of higher-order chromatin structure organization.
Highlights
Immediate early genes (IEGs) are a set of cellular genes, and transcription of mRNAs from which is rapidly induced by both extracellular and intracellular signals through several factors which does not requires de novo protein synthesis[1]
The Early growth response 1 (EGR1) transcription level in CCCTC-binding factor (CTCF) KD cells had decreased to less than 30% of that in the control cells at 2 h post release (Fig. 1B). These results indicate that CTCF is a positive regulator of EGR1 transcription in early G1 phase
We examined the pre-mRNA level of CCND1 gene which is expressed in G1 phase and has putative CTCF binding sites[18]
Summary
Immediate early genes (IEGs) are a set of cellular genes, and transcription of mRNAs from which is rapidly induced by both extracellular and intracellular signals through several factors which does not requires de novo protein synthesis[1]. QPCR was performed with primers for amplification of DNA including CTCF binding sites located the 1.2 kb upstream of the EGR1 gene transcription start site (TSS). DCas9-mediated interference of the formation of higher-order chromatin structure in early G1 phase reduced EGR1 transcription. Chromatin Immunoprecipitation (ChIP) and Chromosome Conformation Capture (3 C) analyses indicated that CTCF-mediated higher-order chromatin structure is formed among the promoter and the upstream and the downstream CTCF-binding sites of the EGR1 gene locus after mitotic exit. These results suggest that CTCF is important for the temporal transcription regulation of EGR1 through its function in the organization of higher-order chromatin structure
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