A conserved protein motif is required for full modulatory activity of negative elongation factor subunits NELF-A and NELF-B in modifying glucocorticoid receptor-regulated gene induction properties

Min Luo, Xinping Lu, Rong Zhu, Zhenhuan Zhang, Carson C. Chow, Rong Li, Simons Stoney

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

NELF-B is a BRCA1-interacting protein and subunit (with NELF-A, -C/D, and-E) of the human negative elongation factor (NELF) complex, which participates in RNApolymerase II pausing shortly after transcription initiation, especially for synchronized gene expression. We now report new activities of NELF-B and other NELF complex subunits, which are to attenuate glucocorticoid receptor (GR)-mediated gene induction, reduce the partial agonist activity of an antagonist, and increase the EC50of an agonist during nonsynchronized expression of exogenous and endogenous reporters. Stable knockdown of endogenous NELF-B has the opposite effects on an exogenous gene. The GR ligand-binding domain suffices for these biological responses. ChIP assays reveal that NELF-B diminishes GR recruitment to promoter regions of two endogenous genes. Using a new competition assay, NELF-A and NELF-B are each shown to act independently as competitive decelerators at two steps after the site of GR action and before or at the site of reporter gene activity. A common motif in each NELF was identified that is required for full activity of both NELF-A and NELF-B. These studies allow us to position the actions of two new modulators of GR-regulated transactivation, NELF-A and NELF-B, relative to other factors in the overall gene induction sequence.

Original languageEnglish (US)
Pages (from-to)34055-34072
Number of pages18
JournalJournal of Biological Chemistry
Volume288
Issue number47
DOIs
StatePublished - Nov 22 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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