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| | Diagram created by M. Oberley. |
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| Description | The predominately expressed isoform is 282 amino acids, and is . The DNA binding domain is thought to be between aa 50 and 129. It has a DEF box between aa 95 to 195. The dimerization domain is thought to reside between aa 130 and 222. There is a leucine zipper domain between aa 143 and 164. The transcriptional repression domain is located on the C terminus from aa 173 to 281. The N-terminal 1-75 aa are missing in isoform B which is predicted to be 206 AA. |
| Expression | Ubiquitous, though more highly expressed in the placenta, skeletal muscle, heart, ovary, kidney, small intestine and spleen. |
| Localisation | Nuclear |
| Function | Heterodimerization with DP1 or 2 creates a sequence specific transcriptional repressor. Overexpression of E2F6 can delay the exit of cells from S-phase, indicating a role for E2F6 in cell-cycle control. E2F6 has been shown via yeast two hybrid and co-IPs to interact with members of the polycomb repressive complex 1, such as Bmi1, RYBP, RING1, MEL-18, and Mph1. The functional outcome of these interactions are as of yet unclear. E2F6 has been biochemically purified in a complex containing polycomb group members h-1(3) mbt like protein, RING1, RING2, hMBLR, as well as YAF and HP1g; this complex also contained a novel euchromatic histone methyltransferase (Eu-HMTase1). This finding led to speculation that E2F6 controlled cellular entry into quiescence, but E2F6 nullizygous MEFs had no kinetic changes or defects in their ability to enter quiescence, or to re-enter into the cell-cycle. However, these animals had homeotic transformations of the axial skeleton, a phenotype that resembled Bmi1 nullizygous mice. This implicated E2F6 in regulation of normal development. |
| Homology | E2F6 has homology with E2Fs1-5 in the DNA-binding domain, the dimerization domain, and the marked box domain located between aa 231 and 239. |
| An E2F-like repressor of transcription. |
| Morkel M, Wenkel J, Bannister AJ, Kouzarides T, Hagemeier C |
| Nature. 1997 ; 390 (6660) : 567-568. |
| PMID 9403682 |
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| E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription. |
| Cartwright P, Mˆºller H, Wagener C, Holm K, Helin K |
| Oncogene. 1998 ; 17 (5) : 611-623. |
| PMID 9704927 |
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| Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6. |
| Gaubatz S, Wood JG, Livingston DM |
| Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (16) : 9190-9195. |
| PMID 9689056 |
| |
| E2F-6, a member of the E2F family that can behave as a transcriptional repressor. |
| Trimarchi JM, Fairchild B, Verona R, Moberg K, Andon N, Lees JA |
| Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (6) : 2850-2855. |
| PMID 9501179 |
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| Molecular cloning and characterization of the mouse E2F6 gene. |
| Kherrouche Z, Begue A, Stehelin D, Montˆ© D |
| Biochemical and biophysical research communications. 2001 ; 288 (1) : 22-33. |
| PMID 11594747 |
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| The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex. |
| Trimarchi JM, Fairchild B, Wen J, Lees JA |
| Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (4) : 1519-1524. |
| PMID 11171983 |
| |
| Two different E2F6 proteins generated by alternative splicing and internal translation initiation. |
| Dahme T, Wood J, Livingston DM, Gaubatz S |
| European journal of biochemistry / FEBS. 2002 ; 269 (20) : 5030-5036. |
| PMID 12383262 |
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| A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. |
| Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y |
| Science (New York, N.Y.). 2002 ; 296 (5570) : 1132-1136. |
| PMID 12004135 |
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| Homeotic transformations of the axial skeleton that accompany a targeted deletion of E2f6. |
| Storre J, Elsˆ§sser HP, Fuchs M, Ullmann D, Livingston DM, Gaubatz S |
| EMBO reports. 2002 ; 3 (7) : 695-700. |
| PMID 12101104 |
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| Sibling rivalry in the E2F family. |
| Trimarchi JM, Lees JA |
| Nature reviews. Molecular cell biology. 2002 ; 3 (1) : 11-20. |
| PMID 11823794 |
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| Dynamic recruitment of NF-Y and histone acetyltransferases on cell-cycle promoters. |
| Caretti G, Salsi V, Vecchi C, Imbriano C, Mantovani R |
| The Journal of biological chemistry. 2003 ; 278 (33) : 30435-30440. |
| PMID 12771133 |
| |
| E2F6 negatively regulates BRCA1 in human cancer cells without methylation of histone H3 on lysine 9. |
| Oberley MJ, Inman DR, Farnham PJ |
| The Journal of biological chemistry. 2003 ; 278 (43) : 42466-42476. |
| PMID 12909625 |
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