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E2F6 E2F transcription factor 6

Identity

Other namesE2F-6
E2F transcription factor 6
E2 Binding Factor 6
HGNC (Hugo) E2F6
Location 2p25.1
Location_base_pair Starts at 11501952 and ends at 11523748 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

Description In humans, E2F6 has 8 exons that span 20881 bp of genomic sequence. It has an ORF of 843 nt.
Transcription There have been 5 mRNA splice variants identified in humans.
  • Transcript variant 1 is the predominant transcript, and it encodes the longest mRNA isoform (a), which is 2342 bp.
  • Transcript variant 2 contains an additional segment (2413 bp mRNA), compared to variant 1, that causes a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform b) is much shorter than isoform a. Transcript variants 2 and 4 encode isoform b.
  • Transcript variant 3 lacks a segment (2287 bp mRNA), compared to variant 1, that causes a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform c) is much shorter than isoform a.
  • Transcript variant 4 contains two additional segments (2546 bp mRNA), compared to variant 1, that cause a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform b) is much shorter than isoform a.
  • Transcript variant 5 contains an additional segment (2475 bp mRNA), compared to variant 1, that causes a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform d) is much shorter than isoform a.
    • Pseudogene There is an E2F6 pseudogene located on chromosome 22q11.2 (LOC376818) containing 2144 bp of the E2F6 gene with no introns.

    Protein

     
      Diagram created by M. Oberley.
    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.

    Mutations

    Note A synthetic mutation in aa 68; L->E: reduced E2F6 transcriptional repressor activity by abrogating DNA binding, but had little effect on S-phase entry.

    Implicated in

    Entity Development
    Note E2F6 is required for normal homeotic development in murine models as mice nullizygous for E2F6 display transformations in the axial skeleton.
    Disease None known.
      

    External links

    Nomenclature
    HGNC (Hugo)E2F6   3120
    Entrez_Gene (NCBI)E2F6  1876  E2F transcription factor 6
    Cards
    AtlasE2F6ID521
    GeneCards (Weizmann)E2F6
    Ensembl (Hinxton)ENSG00000169016 [Gene_View]  E2F6 [Vega]
    AceView (NCBI)E2F6
    Genatlas (Paris)E2F6
    euGene (Indiana)1876
    SOURCE (Stanford)NM_198256
    Gene Expression (Array Express) ENSG00000169016
    Genomic and cartography
    GoldenPath (UCSC)E2F6  -  2p25.1   chr2:11501952-11523748 -  2p25.1   [Description]    (hg18-Mar_2006)
    EnsemblE2F6 - 2p25.1 [CytoView]
    Mapping of homologs : NCBIE2F6 [Mapview]
    OMIM602944   
    Gene and transcription
    Gene : Genbank (Entrez)AF041381 AF059292 AF088059 AK096197 AK223159
    Reference sequence (RefSeq transcript) :SRSNM_198256
    Reference transcript : EntrezNM_198256
    RefSeq genomic : SRSAC_000045 AC_000134 NC_000002 NT_005334 NW_001838766 NW_927719
    RefSeq genomic : EntrezAC_000045 AC_000134 NC_000002 NT_005334 NW_001838766 NW_927719
    Consensus coding sequences : CCDS NCBIE2F6
    Cluster EST : UnigeneHs.603093 [ SRS ] Hs.603093 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)1415
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtO75461 (SRS) O75461 (Expasy) O75461 (Uniprot)
    With graphics : InterProO75461
    Splice isoforms : VarSplice FASTAO75461(VarSplice FASTA)
    Domains : Interpro (SRS)E2F    E2F_TDP    Transcription_factor_E2F6    Wing_hlx_DNA_bd   
    Domains : Interpro (EBI)E2F    E2F_TDP    Transcription_factor_E2F6    Wing_hlx_DNA_bd   
    Related proteins : CluSTrO75461
    Domain families : Pfam SRSE2F_TDP (PF02319)   
    Domain families : Pfam SangerE2F_TDP (PF02319)   
    Domain families : Pfam NCBIpfam02319   
    Blocks (Seattle)O75461
    Crystal structure of protein : PDB SRS
    Crystal structure of protein : PDBSum
    Crystal structure of protein : IMB
    Crystal structure of protein : PDB RSDB
    HPRD04251
    Protein Interaction databases
    DIP (DOE-UCLA)O75461
    IntAct (EBI)O75461
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBIE2F6
    SNP : GeneSNP UtahE2F6
    SNP : HGBaseE2F6
    Genetic variants : HAPMAPE2F6
    Somatic Mutations in Cancer : COSMICE2F6 
    Mutations and Diseases : HGMDE2F6
    Hereditary diseases : OMIM602944   
    Hereditary diseases : GENETests602944   
    Diseases : Genetic AssociationE2F6
    General knowledge
    Homologs : HomoloGeneE2F6
    Homology/Alignments : Family Browser UCSCE2F6
    Phylogenetic Trees/Animal Genes : TreeFamE2F6
    Chemical/Protein Interactions : CTD1876
    Keywords Ontology : AmiGOregulation of transcription involved in G1/S-phase of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  transcription factor activity  transcription corepressor activity  nucleus  transcription factor complex  regulation of transcription, DNA-dependent  cell cycle  MLL1 complex  
    Keywords Ontology : EGO-EBIregulation of transcription involved in G1/S-phase of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  transcription factor activity  transcription corepressor activity  nucleus  transcription factor complex  regulation of transcription, DNA-dependent  cell cycle  MLL1 complex  
    Pathways : BIOCARTA
    Pathways : KEGG
    Other databases
    Probes
    Probes : ImagenesE2F6 Related clones (RZPD - Berlin)
    Literature
    PubMed27 Pubmed reference(s) in Entrez
    PubGeneE2F6

    Bibliography

    An E2F-like repressor of transcription.
    Morkel M, Wenkel J, Bannister AJ, Kouzarides T, Hagemeier C
    Nature. 1997 ; 390 (6660) : 567-568.
    PMID 9403682
     
    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
     
    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
     
    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
     
    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
     
    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
     
    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
     
    Sibling rivalry in the E2F family.
    Trimarchi JM, Lees JA
    Nature reviews. Molecular cell biology. 2002 ; 3 (1) : 11-20.
    PMID 11823794
     
    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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    Contributor(s)

    Written03-2004Matthew Oberley
    McArdle Laboratory for Cancer Research, University of Wisconsin - Madison, 1400 University Ave. Madison, WI 53706, USA

    Citation

    This paper should be referenced as such :
    Oberley M . E2F6 E2F transcription factor 6. Atlas Genet Cytogenet Oncol Haematol. March 2004 .
    URL : http://AtlasGeneticsOncology.org/Genes/E2F6ID521.html

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    indexed on : Sat Feb 27 10:53:46 CET 2010
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