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Arf induction by Tgfβ is influenced by Sp1 and C/ebpβ in opposing directions

Yanbin Zheng1, Caitlin Devitt, Jing Liu

  • 1Division of Hematology-Oncology, Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, Texas, USA. Yanbin.Zheng@UTSouthwestern.edu

Plos One
|August 14, 2013
PubMed

Insights

Transforming growth factor beta (Tgfβ) regulates Arf expression in mouse eye development by decreasing C/ebpβ and increasing Sp1 transcription factors. These findings reveal key regulators of Arf in ocular development.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Oncology

Background:

  • Arf is a tumor suppressor crucial for mouse eye development.
  • Transforming growth factor beta (Tgfβ) signaling is essential for Arf promoter activation during eye development, involving Smad2/3 and p38 MAPK pathways.

Purpose of the Study:

  • To investigate the role of transcription factors in Tgfβ-mediated Arf induction during mouse eye development.
  • To identify proteins that bind near the Arf transcription start site and are affected by Tgfβ signaling.

Main Methods:

  • Utilized mouse embryo fibroblasts (MEFs) and developing mouse eyes.
  • Employed chromatin immunoprecipitation (ChIP) assays.
  • Performed RNA interference (RNAi) and chemical inhibition studies.

Main Results:

  • Tgfβ induction of Arf correlated with decreased expression and DNA binding of C/ebpβ.
  • Ectopic C/ebpβ expression inhibited Tgfβ-induced Arf expression, while C/ebpβ loss increased basal Arf levels.
  • Tgfβ treatment led to increased Sp1 binding to the Arf promoter, which was essential for Arf induction.

Conclusions:

  • C/ebpβ acts as a negative regulator of Arf, while Sp1 functions as a positive regulator.
  • Tgfβ influences Arf expression by modulating the activity of C/ebpβ and Sp1 in mouse eye development.

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