E2F7 represses a transcriptional network of oscillating cell cycle genes to control S-phase progression.

E2F transcription factors are known to be important for timely activation of G1/S and G2/M genes required for cell cycle progression, but transcriptional mechanisms for deactivation of cell cycle regulated genes are unknown. Here, we show that E2F7 is highly expressed during mid to late S-phase, occupies promoters of G1/S regulated genes and represses its transcription. ChIP-seq analysis revealed that E2F7 binds preferentially to genomic sites containing the TTCCCGCC motif, which closely resemble the E2F consensus site. We identified 89 target genes that carry E2F7 binding sites close to the transcriptional start site and that are directly repressed by short term induction of E2F7. Most of these target genes are known to be activated by E2Fs and are involved in DNA replication, metabolism and DNA repair. Importantly, induction of E2F7 during G0-G1/S resulted in S-phase arrest and DNA damage, whereas expression of E2F7 during G2/M failed to disturb cell cycle progression. These findings provide strong evidence that E2F7 controls directly the downswing of oscillating G1/S genes during S-phase progression. 2 samples: E2F7 ChIP-seq and input control, E2F7 ChIP-seq sample was sequenced in 2 independent runs and data were combined for the analysis. Additional sample on Dec. 29, 2015: E2F8 ChIP-seq sample.

E2F转录因子（E2F transcription factors）已知对细胞周期进程所需的G1/S及G2/M基因的适时激活至关重要，但细胞周期调控基因的去激活转录机制至今仍不明晰。本研究发现，E2F7在S期中晚期呈高表达状态，可结合G1/S调控基因的启动子并抑制其转录。染色质免疫共沉淀测序（ChIP-seq）分析显示，E2F7优先结合含有TTCCCGCC基序的基因组位点，该基序与E2F共识结合位点高度相似。本研究共鉴定出89个靶基因，这些基因在转录起始位点附近带有E2F7结合位点，且可通过短期诱导E2F7表达被直接抑制。此类靶基因大多已知可被E2F家族成员激活，并参与DNA复制、代谢及DNA修复过程。值得注意的是，在G0-G1/S期诱导E2F7表达可引发S期阻滞与DNA损伤，而在G2/M期表达E2F7则不会干扰细胞周期进程。上述研究结果提供了有力证据，证明E2F7可在S期进程中直接调控振荡表达的G1/S基因的下调过程。本数据集包含2组样本：E2F7 ChIP-seq样本与输入对照（input control），其中E2F7 ChIP-seq样本经2次独立测序后合并数据用于分析。额外样本采集于2015年12月29日：E2F8 ChIP-seq样本。