HGNC Approved Gene Symbol: E2F6
Cytogenetic location: 2p25.1 Genomic coordinates (GRCh38): 2:11,444,375-11,466,161 (from NCBI)
The E2F family of proteins plays a pivotal role in the regulation of cellular proliferation by controlling the expression of genes that are essential for either entry into, or passage through, the cell cycle. See 600659. To identify additional E2F family members, Trimarchi et al. (1998) searched an EST database for cDNAs that contain a conserved motif from the C-terminal half of the E2F DNA-binding domain. They recovered related mouse and human cDNAs encoding a protein that they called E2F6. Northern blot analysis revealed that E2F6 is expressed as 2 mRNAs, 2.5 and 3.5 kb, in all human tissues and cell lines tested. Antibodies against the protein recognized a 35-kD protein in all tested cell lines on Western blots. The predicted human and mouse E2F6 protein sequences are 92% identical. The DNA-binding and dimerization domains of E2F6 are highly related to those of other E2F family members, but this protein lacks the sequences necessary for either transcriptional activation or binding to RB1 (614041), p107 (RBL1; 116957), or p130 (RBL2; 180203). Trimarchi et al. (1998) found that E2F6 can dimerize with either DP1 (189902) or DP2 (602160) and that the resultant complexes can bind to DNA in a sequence-specific manner, confirming that it is a genuine member of the E2F family. However, since E2F6 is unable to activate transcription and is not regulated by RB1, p107, or p130, Trimarchi et al. (1998) suggested that E2F6 can act to repress the transcription of E2F-responsive genes by countering the activity of other E2F complexes.
E2F6 contributes to gene silencing in a manner independent of retinoblastoma protein family members. To better elucidate the molecular mechanism of repression by E2F6, Ogawa et al. (2002) purified the factor from cultured cells. E2F6 is found in a multimeric protein complex that contains MGA (616061) and MAX (154950), and thus the complex can bind not only to the E2F binding site but also to MYC- (190080) and Brachyury- (601397) binding sites. Moreover, the complex contains chromatin modifiers such as a novel histone methyltransferase (607001) that modifies lysine-9 of histone H3 (602810), HP1-gamma (604477), and Polycomb group proteins. The E2F6 complex preferentially occupies target promoters in G0 cells rather than in G1 cells. Ogawa et al. (2002) concluded that these chromatin modifiers contribute to silencing of E2F- and MYC-responsive genes in quiescent cells.
Ogawa, H., Ishiguro, K., Gaubatz, S., Livingston, D. M., Nakatani, Y. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science 296: 1132-1136, 2002. [PubMed: 12004135] [Full Text: https://doi.org/10.1126/science.1069861]
Trimarchi, J. M., Fairchild, B., Verona, R., Moberg, K., Andon, N., Lees, J. A. E2F-6, a member of the E2F family that can behave as a transcriptional repressor. Proc. Nat. Acad. Sci. 95: 2850-2855, 1998. [PubMed: 9501179] [Full Text: https://doi.org/10.1073/pnas.95.6.2850]