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Symbol E2F4 contributors: mct - updated : 05-04-2018
HGNC name E2F transcription factor 4, p107/p130-binding
HGNC id 3118
Location 16q22.1      Physical location : 67.226.067 - 67.232.820
Synonym name
  • p107/p130-binding protein
  • E2F transcription factor 4
  • Synonym symbol(s) E2F-4
    TYPE functioning gene
    STRUCTURE 6.75 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   triplet
    text structure
  • CAG repeat in exon 7
  • coding region of the E2F4 gene contains a longer spacer segment of a CAG trinucleotide repeat sequence encoding 13 consecutive serine residues, which is highly vulnerable to frameshift mutations in situations of genetic instability (
  • E2F4 promoter occupancy is globally associated with TP53-repression targets, but not with TP53 activation targets, implicating E2F4 complexes as effectors of CDKN1A-dependent TP53-mediated repression
  • MAPPING cloned Y linked   status provisional
    Map cen - D16S2846 - D16S318 - E2F4 - D16S421 - D16S322 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2100 - 413 - 2007 17656449
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Endocrineparathyroid   highly
    Lymphoid/Immunelymph node   highly
    Nervousbrain   moderately
    Reproductivefemale systemuteruscervix highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period pregnancy
    Text placenta
  • a DNA binding domain,
  • a leucine zipper and a pRB binding domains
    interspecies homolog to murine E2f4
  • E2F/DP family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    text cytoplasmic in quiescent differentiated cells but nuclear in proliferative cells
    basic FUNCTION
  • involved in cell proliferation
  • controlling genes regulating S phase entry and DNA synthesis
  • playing a critical role in the control of maturation cell in multiple cellular lineages (in mouse)
  • could exert a strong influence over the susceptibility to oncogenic transformation
  • acting to repress E2F-responsive genes, and having a strong capacity to inhibit transformation
  • may play an oncogenic rather than a tumor suppressor role in cells
  • in response to radiation, becomes active in the nucleus, enforces a stable G(2) arrest by target gene repression, and thus provides increased cell survival ability by minimizing propagation of cells that have irreparable DNA damage
  • induces cell death via multiple pathways in normal intestinal epithelial crypt cells but not in colon cancer cells (full mitogenic potential)
  • involved in gene repression and cell cycle exit, and also has poorly understood effects in differentiation
  • important in early stages of commitment to the lymphoid lineage
  • nuclear E2F4 may be determinant in the promotion of proliferation of human intestinal epithelial crypt cells and colorectal cancer cells
  • is required for cardiomyocyte proliferation, suggesting a function for E2F4 in mitosis
  • E2F4 and RB1 play independent cell-intrinsic roles in fetal erythropoiesis
  • involved in gene repression
  • is implicated in maintaining the G(0)/G(1) cell cycle state via transcriptional repression of genes that encode proteins required for S-phase progression
  • plays an important role in enabling osteoblast progenitors to exit the cell cycle and subsequently differentiate thereby contributing to the commitment of these cells to the bone lineage
  • can inhibit hypoxia-induced cell death in isolated ventricular cardiomyocytes
  • essential negative function of E2F4 in cardiac myocyte apoptosis
  • plays a critical role in cell cycle progression of normal and cancerous intestinal epithelial cells
  • believed to exhibit crucial control over the maintenance of a differentiated state of neurons
  • in contrast to E2F1 and E2F3, which sensitize to death, E2F4 plays a crucial protective role in neuronal death evoked by DNA damage, hypoxia, and global ischemic insult
  • likely plays a protective role in neurons from ischemic insult by forming repressive complexes that prevent prodeath factors such as Myb from being expressed
  • E2F4 and E2F5 display overlapping roles in controlling the normal development of the male reproductive system
  • MCIDAS and activated E2F4 induce multiciliated cell differentiation in primary fibroblasts
  • CELLULAR PROCESS cell cycle
    nucleotide, transcription
    a component
  • complex MADH3/E2F4/E2F5/DP1/RBL1
  • linking the TGFB receptor to CMYC repression
  • E2F4-RBL2 transcriptional repressor complex is a cell-cycle inhibitor in mitotic cells
    small molecule
  • binds directly to the proximal promoter of the Rb gene
  • cellular function of CDKN1B as a transcriptional regulator in association with RBL2/E2F4 complexes that could be relevant for tumorigenesis
  • TRIM28 has anti-proliferative activity in lung cancers via repression of E2F3, E2F4 that are critical for cell proliferation
  • cooperated with E2F4 to promote a state of deepened repression at cell cycle genes during differentiation
  • by coopting E2F4, E2F5 regulation of cell cycle genes, MCIDAS drives massive centriole assembly in epithelial progenitors in a manner required for multiciliate cell differentiation
  • gain of function mutant TP53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene expression
  • PHF8 by controlling E2F4 expression maintains endothelial function
  • cell & other
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate cancer
    tumoral somatic mutation      
    in adult cell leukemia and childhood acute lymphoid leukemia
    Variant & Polymorphism
    Candidate gene
    Therapy target
    inhibiting transcription factors E2F4 and E2F5 having possible usefulness as targets in anti-cancer therapy
    E2F4 is a target for developing novel and less toxic treatments for sporadic Burkitt lymphoma (sBL)