Regular Article
Nonredundant Roles of the Elongation Factor MEN in Postimplantation Development

https://doi.org/10.1006/bbrc.2000.3970Get rights and content

Abstract

The MEN/ELL gene was cloned as a fusion partner of the MLL gene in the t(11;19)(q23;p13.1) translocation, which is found in adult myeloid leukemia. MEN belongs to a family of RNA polymerase II elongation factors and dysregulated production of MEN through the MLL promoter could cause malignant transformation of myeloid cells. To pursue the physiological role and determine the requirement of the MEN gene product in mouse development, we generated knockout mice (MEN−/−) by gene targeting in embryonic stem cells. After intercrossing heterozygous mice to generate homozygous mutants, we identified no homozygotes (MEN−/−) even at E9.5, as well as after birth, by Southern analysis. Moreover, histological examinations revealed degenerative changes in nearly one-fourth of E6.5 embryos, which were gradually resorbed by E8.5. Our findings demonstrated that MEN−/− mice are embryonic lethal, and die before E6.5 and after implantation. MEN should play a nonredundant role in postimplantation development of mice.

References (26)

  • N. Shinobu et al.

    Physical interaction and functional antagonism between the RNA polymerase II elongation factor ELL and p53

    J. Biol. Chem.

    (1999)
  • A. Shilatifard et al.

    An RNA polymerase II elongation factor encoded by the human ELL gene

    Science

    (1996)
  • Cited by (22)

    • Regulation of fertility, survival, and cuticle collagen function by the Caenorhabditis elegans eaf-1 and ell-1 genes

      2011, Journal of Biological Chemistry
      Citation Excerpt :

      ELL has been identified in an array of species, including yeast (10), Drosophila (11), zebrafish (12), mouse (13), and human (14). This widely expressed gene is essential for embryonic development because deletion of ELL in mouse or Drosophila causes embryonic lethality (15, 16). ELL also plays an important role in leukemia (8, 17).

    • Defective FESTA/EAF2-mediated transcriptional activation in S-II-deficient embryonic stem cells

      2007, Biochemical and Biophysical Research Communications
      Citation Excerpt :

      Thus, stimulation of transcription elongation by Elongin A and that by S-II might have distinct roles in regulating cellular growth. Other transcription elongation factors, such as ELL and Spt5, are required at specific developmental steps [19,20], suggesting that the transcription of some genes is preferentially affected in the absence of each transcription elongation factor. In yeast S-II mutants, the transcriptional induction of two genes, SDT1/SSM1 and IMD2/PUR5, is specifically impaired in response to nucleotide-depleting drugs such as 6-azauracil and mycophenolic acid [21,22].

    • FB1, an E2A fusion partner in childhood leukemia, interacts with U19/EAF2 and inhibits its transcriptional activity

      2007, Cancer Letters
      Citation Excerpt :

      ELL and EAF1 are components of the Cajal bodies (CB) [21], raising a possibility that FB1 may be also present in the Cajal Bodies. ELL is essential in early animal development because ELL gene knockout in the mouse resulted in embryonic lethality [22]. ELL is also involved in tumor development because MLL–ELL translocation occurs in acute myeloid leukemia.

    View all citing articles on Scopus
    1

    Present address: Department of Hematology, Dokkyo University School of Medicine, Tochigi, Japan.

    2

    To whom correspondence should be addressed at Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. Fax: +81-3-5689-7286. E-mail: [email protected].

    View full text