Transcription elongation regulator 1 is a co-integrator of the cell fate determination factor Dachshund homolog

Jie Zhou, Yang Liu, Wei Zhang, Vladimir M. Popov, Min Wang, Nagarajan Pattabiraman, Carlos Suñé, Ales Cvekl, Kongming Wu, Jie Jiang, Chenguang Wang, Richard G. Pestell

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

DACH1 (Dachshund homolog 1) is a key component of the retinal determination gene network and regulates gene expression either indirectly as a co-integrator or through direct DNA binding. The current studies were conducted to understand, at a higher level of resolution, the mechanisms governing DACH1-mediated transcriptional repression via DNA sequence-specific binding. DACH1 repressed gene transcription driven by the DACH1-responsive element (DRE). Recent genome-wide ChIP-Seq analysis demonstrated DACH1 binding sites co-localized with Forkhead protein (FOX) binding sites. Herein, DACH1 repressed, whereas FOX proteins enhanced, both DRE and FOXA-responsive element-driven gene expression. Reduced DACH1 expression using a shRNA approach enhanced FOX protein activity. As DACH1 antagonized FOX target gene expression and attenuated FOX signaling, we sought to identify limiting co-integrator proteins governing DACH1 signaling. Proteomic analysis identified transcription elongation regulator 1 (TCERG1) as the transcriptional coregulator of DACH1 activity. The FF2 domain of TCERG1 was required for DACH1 binding, and the deletion of FF2 abolished DACH1 trans-repression function. The carboxyl terminus of DACH1 was necessary and sufficient for TCERG1 binding. Thus, DACH1 represses gene transcription through direct DNA binding to the promoter region of target genes by recruiting the transcriptional co-regulator, TCERG1.

Original languageEnglish (US)
Pages (from-to)40342-40350
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number51
DOIs
StatePublished - Dec 17 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Zhou, J., Liu, Y., Zhang, W., Popov, V. M., Wang, M., Pattabiraman, N., Suñé, C., Cvekl, A., Wu, K., Jiang, J., Wang, C., & Pestell, R. G. (2010). Transcription elongation regulator 1 is a co-integrator of the cell fate determination factor Dachshund homolog. Journal of Biological Chemistry, 285(51), 40342-40350. https://doi.org/10.1074/jbc.M110.156141