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E2F6 (E2F transcription factor 6)

Written2004-03Matthew Oberley
McArdle Laboratory for Cancer Research, University of Wisconsin - Madison, 1400 University Ave. Madison, WI 53706, USA

(Note : for Links provided by Atlas : click)

Identity

Other aliasE2F-6
E2F transcription factor 6
E2 Binding Factor 6
LocusID (NCBI) 1876
Atlas_Id 521
Location 2p25.1  [Link to chromosome band 2p25]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
E2F6 (2p25.1) / HLA-DRB1 (6p21.32)E2F6 (2p25.1) / LYRM4 (6p25.1)E2F6 (2p25.1) / PDIA6 (2p25.1)
GREB1 (2p25.1) / E2F6 (2p25.1)

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

    Note
      
    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.
      

    Bibliography

    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
     
    E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription.
    Cartwright P, Müller H, Wagener C, Holm K, Helin K
    Oncogene. 1998 ; 17 (5) : 611-623.
    PMID 9704927
     
    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
     
    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
     
    Molecular cloning and characterization of the mouse E2F6 gene.
    Kherrouche Z, Begue A, Stehelin D, Monté D
    Biochemical and biophysical research communications. 2001 ; 288 (1) : 22-33.
    PMID 11594747
     
    An E2F-like repressor of transcription.
    Morkel M, Wenkel J, Bannister AJ, Kouzarides T, Hagemeier C
    Nature. 1997 ; 390 (6660) : 567-568.
    PMID 9403682
     
    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
     
    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, Elsässer 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
     

    Citation

    This paper should be referenced as such :
    Oberley, M
    E2F6 (E2F transcription factor 6)
    Atlas Genet Cytogenet Oncol Haematol. 2004;8(2):63-64.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/E2F6ID521.html


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
      t(2;2)(p25;p25) GREB1/E2F6
    t(2;2)(p25;p25) GREB1/E2F6


    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
      t(2;6)(p25;p25) E2F6/LYRM4


    External links

    Nomenclature
    Cards
    AtlasE2F6ID521.txt
    Aliases
    Genomic and cartography
    Gene and transcription
    RefSeq transcript (Entrez)
    RefSeq genomic (Entrez)
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    BioGPS (Tissue expression)1876
    Protein : pattern, domain, 3D structure
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Protein Interaction databases
    Ontologies - Pathways
    Clinical trials, drugs, therapy
    Miscellaneous
    canSAR (ICR) (select the gene name)
    Probes
    Litterature
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed


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    indexed on : Thu Oct 18 17:34:31 CEST 2018

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