E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints.

By Bing Ren, Hieu Cam, Yasuhiko Takahashi, T. Volkert, Jolyon Terragni, Richard A. Young, B. Dynlacht. Genes & Development, 2002

1,248 citations recorded by the source corpus.

The E2F transcription factor family is known to play a key role in the timely expression of genes required for cell cycle progression and proliferation, but only a few E2F target genes have been identified. We explored the possibility that E2F regulators play a broader role by identifying additional genes bound by E2F in living human cells. A protocol was developed to identify genomic binding sites for DNA-binding factors in mammalian cells that combines immunoprecipitation of cross-linked protein-DNA complexes with DNA microarray analysis. Among approximately 1200 genes expressed during cell cycle entry, we found that the promoters of 127 were bound by the E2F4 transcription factor in primary fibroblasts. A subset of these targets was also bound by E2F1. Most previously identified target genes known to have roles in DNA replication and cell cycle control and represented on the microarray were confirmed by this analysis. We also identified a remarkable cadre of genes with no previous connection to E2F regulation, including genes that encode components of the DNA damage checkpoint and repair pathways, as well as factors involved in chromatin assembly/condensation, chromosome segregation, and the mitotic spindle checkpoint. Our data indicate that E2F directly links cell cycle progression with the coordinate regulation of genes essential for both the synthesis of DNA as well as its surveillance.

Subfields: Cell Biology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/a4f188e3305a9bc3a029f057f87a590026f6bf64

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Citations in the corpus

Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. (2004, background): “Extrapolating these findings to the whole genomecells have involved selected upstream regions (Horak et al., 2002b; Mao et al., 2003; Ren et al., 2002) and predicts a total of about 12,000 Sp1 sites, 25,000 cMyc sites, and 1600 p53 sites.hence do not address the possibility of transcription factor…”
Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. (2005, methodology): “Ligation-Mediated PCR was performed as previously described (Ren et al., 2002).”
Mapping of genetic and epigenetic regulatory networks using microarrays (2005, background): “The cell cycle regulator E2F4 was found to bind to 2–3% of ∼13,000 tested promoters in quiescent cell”
Ki-67: more than a proliferation marker (2018, background): “One of the E2F target genes is MKI67, encoding Ki-67 (Ishida et al. 2001; Ren et al. 2002; Tian et al. 2011).”
Genomic targets of the human c-Myc protein. (2003, methodology): “The same strategy has been used to identify target genes of human E2F (Ren et al. 2002; Weinmann et al. 2002) but, as in our present work, only a fraction of all possible binding sites was covered.”
The profile of repeat‐associated histone lysine methylation states in the mouse epigenome (2005, background): “…on defined chromosomal loci (Litt et al, 2001; Noma et al, 2001), parts of entire chromosomes (Greil et al, 2003; Lippman et al, 2004) and with genome-wide but promoter-biased or EST sequences that were displayed on microarrays (Ren et al, 2002; Santos-Rosa et al, 2002; Schübeler et al, 2004).”
Toward maintaining the genome: DNA damage and replication checkpoints. (2002, background): “Yeast and mammalian cells indirectly contribute to repair responses by inducing transcription of a number of genes encoding proteins involved in repair (12, 62, 70, 111, 153, 165).”
Core transcriptional regulatory circuitry in human embryonic stem cells. (2005, methodology): “The E2F4 antibody used in this study was obtained from Santa Cruz (sc-1082) and has been shown to recognize E2F4-responsive genes identified in previous ChIP studies (Table S2) (Ren et al., 2002; Weinmann et al., 2002).”