Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins

Young Hwa Goo, Young Chang Sohn, Dae Hwan Kim, Seung Whan Kim, Min Jung Kang, Dong Ju Jung, Eunyee Kwak, Nickolai A. Barlev, Shelley L. Berger, Vincent T. Chow, Robert G. Roeder, David O. Azorsa, Paul S. Meltzer, Pan Gil Suh, Eun Joo Song, Kong Joo Lee, Young Chul Lee, Jae Woon Lee

Research output: Contribution to journalArticle

168 Scopus citations

Abstract

Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. These include activating signal cointegrator 2 (ASC-2), a recently isolated transcriptional coactivator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors and numerous other transcription factors. In this report, we show that ASC-2 belongs to a steady-state complex of approximately 2 MDa (ASC-2 complex [ASCOM]) in HeLa nuclei. ASCOM contains retinoblastoma-binding protein RBQ-3, α/β-tubulins, and trithorax group proteins ALR-1, ALR-2, HALR, and ASH2. In particular, ALR-1/2 and HALR contain a highly conserved 130- to 140-amino-acid motif termed the SET domain, which was recently implicated in histone H3 lysine-specific methylation activities. Indeed, recombinant ALR-1, HALR, and immunopurified ASCOM exhibit very weak but specific H3-lysine 4 methylation activities in vitro, and transactivation by retinoic acid receptor appears to involve ligand-dependent recruitment of ASCOM and subsequent transient H3-lysine 4 methylation of the promoter region in vivo. Thus, ASCOM may represent a distinct coactivator complex of nuclear receptors. Further characterization of ASCOM will lead to a better understanding of how nuclear receptors and other transcription factors mediate transcriptional activation.

Original languageEnglish (US)
Pages (from-to)140-149
Number of pages10
JournalMolecular and cellular biology
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Goo, Y. H., Chang Sohn, Y., Kim, D. H., Kim, S. W., Kang, M. J., Jung, D. J., Kwak, E., Barlev, N. A., Berger, S. L., Chow, V. T., Roeder, R. G., Azorsa, D. O., Meltzer, P. S., Suh, P. G., Song, E. J., Lee, K. J., Lee, Y. C., & Lee, J. W. (2003). Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins. Molecular and cellular biology, 23(1), 140-149. https://doi.org/10.1128/MCB.23.1.140-149.2003