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E2F4 Transcription Factor definition: An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F4 recruits chromatin remodeling factors indirectly to target gene PROMOTER REGIONS through RETINOBLASTOMA LIKE PROTEIN P130 and RETINOBLASTOMA LIKE PROTEIN P107.
 
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10.1371/journal.pone.0001061.g001 Figure 1 Strategy to compare E2F4 bound and E2F4 dependent gene expression in mouse and human. (A) Transcription factor binding was identified in vivo using chromatin immunoprecipitation combined with proximal promoter arrays in three human tissues, a human cell line, seven mouse tissues, and a mouse cell line. (B) Gene expression in the liver, kidney, and testes of littermate mice lacking one or two copies of E2f4 were compared in replicate, and genes specifically perturbed in the adult identified in all three tissues. (C) Analysis approaches identified the genes bound in common among all human and all mouse tissues, those shared between species, and whether any genes were both bound by E2f4 in mouse adult liver, kidney, or testes, and whose expression were altered by removal of E2f4.

Caitlin M. Conboy et al.

PLoS ONE 2 (10), 24 Oct 2007

Selected genes (by category) bound by E2F4 in all human tissues p-value for E2F4 binding Process Gene Full Name Liver Acinar Islets HepG2 Cell Cycle ZWINT ZW10 interactor 4.0E-08 6.0E-08 7.0E-08 4.0E-08 (1×10–44) CCNB1 Cyclin B1 7.0E-08 9.0E-08 2.0E-07 8.0E-08 INCENP Inner centromere protein 2.0E-07 3.0E-07 3.0E-07 2.0E-07 CDC23 Cell division cycle 23 homolog 2.0E-06 3.0E-06 3.0E-06 1.0E-06 CDC6 Cell division cycle 6 homolog 5.0E-08 7.0E-08 9.0E-08 5.0E-08 CDK2 Cyclin-dependent kinase 2 4.0E-06 8.0E-06 5.0E-06 5.0E-06 NEK2 NIMA-related kinase 2 2.0E-05 3.0E-05 2.0E-05 2.0E-05 MAD2L1 MAD2 mitotic arrest deficient-like 1 5.0E-07 1.0E-06 9.0E-07 5.0E-07 CDC45L CDC45 cell division cycle 45-like 3.0E-07 5.0E-07 5.0E-07 3.0E-07 CCNB2 Cyclin B2 2.0E-08 2.0E-08 3.0E-08 3.0E-08 RBL1 Retinoblastoma-like 1 (p107) 3.0E-06 4.0E-06 4.0E-06 3.0E-06 NUDC Nuclear distribution gene C homolog 3.0E-05 4.0E-05 3.0E-05 3.0E-05 E2F3 E2F transcription factor 3 1.0E-05 1.0E-05 1.0E-05 1.0E-05 TCF19 Transcription factor 19 (SC1) 9.0E-07 2.0E-06 2.0E-06 7.0E-07 CCNG2 Cyclin G2 1.0E-07 1.0E-07 2.0E-07 1.0E-07 DNA Replication RFC3 Replication factor C (activator 1) 3 1.0E-06 2.0E-06 2.0E-06 9.0E-07 (4×10–19) PCNA Proliferating cell nuclear antigen 2.0E-06 3.0E-06 3.0E-06 2.0E-06 POLE3 Polymerase epsilon 3 (p17 subunit) 2.0E-05 2.0E-05 2.0E-05 2.0E-05 NUP98 Nucleoporin 98 kDa 1.0E-05 2.0E-05 2.0E-05 2.0E-05 ORC3L Origin recognition complex, subunit 3-like 4.0E-07 5.0E-07 5.0E-07 3.0E-07 RRM1 Ribonucleotide reductase M1 polypeptide 2.0E-07 3.0E-07 3.0E-07 2.0E-07 ORC1L Origin recognition complex, subunit 1-like 7.0E-06 1.0E-05 1.0E-05 8.0E-06 TOP2A Topoisomerase (DNA) II alpha 8.0E-07 1.0E-06 1.0E-06 6.0E-07 RFC5 Replication factor C (activator 1) 5 2.0E-06 4.0E-06 4.0E-06 2.0E-06 BLM Bloom syndrome 7.0E-09 6.0E-09 4.0E-09 6.0E-09 DNA repair DCLRE1C DNA cross-link repair 1C (PSO2 homolog) 4.0E-07 6.0E-07 6.0E-07 4.0E-07 (8×10–18) XRCC1 X-ray repair complementing defective repair 5.0E-07 8.0E-07 7.0E-07 4.0E-07 MLH1 mutL homolog 1 2.0E-06 4.0E-06 4.0E-06 2.0E-06 BRCA1 Breast cancer 1, early onset 2.0E-07 2.0E-07 3.0E-07 2.0E-07 EXO1 Exonuclease 1 6.0E-08 7.0E-08 1.0E-07 6.0E-08 TYMS Thymidylate synthetase 1.0E-07 1.0E-07 2.0E-07 1.0E-07 PMS2 Postmeiotic segregation increased 2 4.0E-05 8.0E-05 6.0E-05 5.0E-05 FEN1 Flap structure-specific endonuclease 1 7.0E-06 1.0E-05 1.0E-05 8.0E-06 NUDT1 Nudix-type motif 1 4.0E-05 7.0E-05 5.0E-05 5.0E-05 RAD51 RecA homolog 1.0E-07 2.0E-07 2.0E-07 2.0E-07 Apoptosis NUDT2 Nudix-type motif 2 2.0E-07 2.0E-07 1.0E-07 9.0E-08 (6×10–6) CASP8AP2 CASP8 associated protein 2 2.0E-05 2.0E-05 2.0E-05 2.0E-05 ITGB3BP Integrin beta 3 binding protein 1.0E-05 2.0E-05 2.0E-05 2.0E-05 TEGT Testis enhanced gene transcript 4.0E-05 6.0E-05 5.0E-05 3.0E-05 NDUFS1 NADH dehydrogenase (ubiquinone) Fe-S 1 3.0E-06 4.0E-06 4.0E-06 3.0E-06 BNIP3L BCL2/adenovirus E1B interacting protein 3-like 4.0E-05 6.0E-05 5.0E-05 4.0E-05 SON SON DNA binding protein 4.0E-05 7.0E-05 5.0E-05 4.0E-05 CFL1 Cofilin 1 (non-muscle) 4.0E-05 6.0E-05 5.0E-05 3.0E-05 GLO1 Glyoxalase I 4.0E-08 6.0E-08 7.0E-08 4.0E-08 CHEK2 CHK2 checkpoint homolog 1.0E-08 8.0E-09 9.0E-09 1.0E-08 RNA processing TTF2 Transcription termination factor 2 2.0E-08 2.0E-08 3.0E-08 3.0E-08 (4×10–8) CSTF3 Cleavage stimulation factor, subunit 3 3.0E-07 5.0E-07 5.0E-07 3.0E-07 HSPC148 Hypothetical protein HSPC148 1.0E-05 2.0E-05 2.0E-05 1.0E-05 SNRPF Small nuclear ribonucleoprotein peptide F 4.0E-05 6.0E-05 5.0E-05 4.0E-05 DIS3 DIS3 mitotic control homolog 4.0E-06 8.0E-06 6.0E-06 5.0E-06 SIP1 survival interacting protein 1 3.0E-05 4.0E-05 4.0E-05 3.0E-05 FTSJ2 FtsJ homolog 2 (E. coli) 3.0E-06 4.0E-06 4.0E-06 3.0E-06 CSTF2T cleavage stimulation factor, subunit 2, tau 9.0E-07 2.0E-06 1.0E-06 7.0E-07 LSM3 LSM3 homolog, U6 sn RNA associated 2.0E-06 3.0E-06 3.0E-06 2.0E-06 SFRS1 splicing factor, arginine/serine-rich 1 2.0E-07 2.0E-07 3.0E-07 2.0E-07 Organized by GO categories, top hits by significance with p-values and binding ratios.

Caitlin M. Conboy et al.

PLoS ONE 2 (10), 24 Oct 2007

10.1371/journal.pone.0001061.g003 Figure 3 Gene expression changes upon germline removal of E2f4 transcription factor binding in mouse liver, kidney, and testes are minimal, and poorly overlap the genes bound in mice containing E2f4. (A) The complete list of genes that were differentially expressed when E2f4 was removed where the proximal promoter of these transcripts was present on the mouse promoter array.

Caitlin M. Conboy et al.

PLoS ONE 2 (10), 24 Oct 2007

Most gene expression changes were tissue-specific, and very few of these genes showed in vivo E2f4 binding. (B) The complete list of genes bound by E2f4 in kidney, liver, and testes, clustered by transcription factor binding in each tissue sequentially.

Caitlin M. Conboy et al.

PLoS ONE 2 (10), 24 Oct 2007

Discussion We have combined gene expression analysis of mice lacking E2f4 with the conservation of transcription factor binding to dissect the conserved regulatory networks controlled by E2F4 that govern cell cycle and proliferation in primary mouse and human tissues.

Caitlin M. Conboy et al.

PLoS ONE 2 (10), 24 Oct 2007

 
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