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In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
10:44

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

Published on: May 5, 2023

Ets-2 interacts with co-repressor BS69 to repress target gene expression

Guo Wei1, Alicia Erbe Schaffner, Kimberly M Baker

  • 1Department of Molecular Genetics, Comprehensive Cancer Center, Ohio State University, 484 W. 12th Ave., Columbus, OH 43210, USA.

Anticancer Research
|August 5, 2003
PubMed
Abstract

Insights

Phosphorylation of Ets-2 (a protein regulating cell growth) influences its interaction with co-repressor BS69, potentially switching Ets-2

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Transcription Factors

Background:

  • The ETS-family of transcription factors (over 30 members) regulates critical cellular processes like growth, differentiation, and survival.
  • Specificity within the ETS-family is poorly understood, with signaling pathway modulation being a key proposed mechanism.
  • Ets-2, an ETS-family member, is known to be modulated by phosphorylation, particularly in its pointed domain.

Purpose of the Study:

  • To investigate how phosphorylation of the Ets-2 pointed domain affects its interactions with other proteins in the nucleus.
  • To elucidate the role of identified interacting proteins in regulating Ets-2 target genes.

Main Methods:

  • Yeast two-hybrid screens to identify Ets-2 interacting proteins.
  • Biochemical assays (in vitro) to characterize protein-protein interactions.
  • Transfection assays to assess gene regulation by Ets-2 and its partners.

Main Results:

  • BS69, a known co-repressor, was identified as an Ets-2 interacting partner.
  • Phosphorylation of the Ets-2 pointed domain reduced its interaction with BS69 in vitro.
  • Co-expression of Ets-2 and BS69 led to repression of specific Ets-2 target genes in transfection assays.

Conclusions:

  • Ets-2 can function as a repressor, requiring BS69 as a co-repressor.
  • Phosphorylation of Ets-2 may alter its function from repressor to activator by disrupting the Ets-2/BS69 complex formation.
  • This study provides insight into the regulatory mechanisms governing ETS-family transcription factor specificity.

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