Masashi Omori

Publications (2)8.21 Total impact

• Article: GABP, HCF-1 and YY1 are involved in Rb gene expression during myogenesis.

  Sophie Deléhouzée, Tatsufumi Yoshikawa, Chika Sawa, Jun-Ichi Sawada, Takumi Ito, Masashi Omori, Tadashi Wada, Yuki Yamaguchi, Yasuaki Kabe, Hiroshi Handa
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  ABSTRACT: Muscle cell differentiation, or myogenesis, is a well-characterized process and involves the expression of specific sets of genes in an orderly manner. A prerequisite for myogenesis is the exit from the cell cycle, which is associated with the up-regulation of the tumor suppressor Rb. In this study, we set to investigate the regulatory mechanism of the Rb promoter that allows adequate up-regulation in differentiating myoblasts. We report that Rb expression is regulated by the transcription factors GABP, HCF-1 and YY1. Before induction of differentiation, Rb is expressed at a low level and GABP and YY1 are both present on the promoter. YY1, which exerts an inhibitory effect on Rb expression, is removed from the promoter as cells advance through myogenesis and translocates from the nucleus to the cytoplasm. On the other hand, upon induction of differentiation, the GABP cofactor HCF-1 is recruited to and coactivates the promoter with GABP. RNAi-mediated knock-down of HCF-1 results in inhibition of Rb up-regulation as well as myotube formation. These results indicate that the Rb promoter is subject to regulation by positive and negative factors and that this intricate activation mechanism is critical to allow the accurate Rb gene up-regulation observed during myogenesis.
  Genes to Cells 08/2005; 10(7):717-31. · 2.68 Impact Factor
• Article: Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex.

  Takashi Narita, Yuki Yamaguchi, Keiichi Yano, Seiji Sugimoto, Sittinan Chanarat, Tadashi Wada, Dong-ki Kim, Jun Hasegawa, Masashi Omori, Naoto Inukai, Masaki Endoh, Tomoko Yamada, Hiroshi Handa
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  ABSTRACT: The multisubunit transcription elongation factor NELF (for negative elongation factor) acts together with DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) sensitivity-inducing factor (DSIF)/human Spt4-Spt5 to cause transcriptional pausing of RNA polymerase II (RNAPII). NELF activity is associated with five polypeptides, A to E. NELF-A has sequence similarity to hepatitis delta antigen (HDAg), the viral protein that binds to and activates RNAPII, whereas NELF-E is an RNA-binding protein whose RNA-binding activity is critical for NELF function. To understand the interactions of DSIF, NELF, and RNAPII at a molecular level, we identified the B, C, and D proteins of human NELF. NELF-B is identical to COBRA1, recently reported to associate with the product of breast cancer susceptibility gene BRCA1. NELF-C and NELF-D are highly related or identical to the protein called TH1, of unknown function. NELF-B and NELF-C or NELF-D are integral subunits that bring NELF-A and NELF-E together, and coexpression of these four proteins in insect cells resulted in the reconstitution of functionally active NELF. Detailed analyses using mutated recombinant complexes indicated that the small region of NELF-A with similarity to HDAg is critical for RNAPII binding and for transcriptional pausing. This study defines several important protein-protein interactions and opens the way for understanding the mechanism of DSIF- and NELF-induced transcriptional pausing.
  Molecular and Cellular Biology 04/2003; 23(6):1863-73. · 5.53 Impact Factor