Serum starvation induces DRAM expression in liver cancer cells via histone modifications within its promoter locus

PLoS One. 2012;7(12):e50502. doi: 10.1371/journal.pone.0050502. Epub 2012 Dec 12.

Abstract

DRAM is a lysosomal membrane protein and is critical for p53-mediated autophagy and apoptosis. DRAM has a potential tumor-suppressive function and is downregulated in many human cancers. However, the regulation of DRAM expression is poorly described so far. Here, we demonstrated that serum deprivation strongly induces DRAM expression in liver cancer cells and a core DNA sequence in the DRAM promoter is essential for its responsiveness to serum deprivation. We further observed that euchromatin markers for active transcriptions represented by diacetyl-H3, tetra-acetyl-H4 and the trimethyl-H3K4 at the core promoter region of DRAM gene are apparently increased in a time-dependent manner upon serum deprivation, and concomitantly the dimethyl-H3K9, a herterochromatin marker associated with silenced genes, was time-dependently decreased. Moreover, the chromatin remodeling factor Brg-1 is enriched at the core promoter region of the DRAM gene and is required for serum deprivation induced DRAM expression. These observations lay the ground for further investigation of the DRAM gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Autophagy / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic*

Substances

  • DRAM1 protein, human
  • Histones
  • Membrane Proteins
  • NF-kappa B

Grants and funding

This work was supported by the Science and Technology Committee of Shanghai Metropolitan (11ZR1423100); the National Science Foundation of China (grant No.: 30772233, 30873057 to Y. Lu, and 81172028 to Z. Hou); Key Basic Project of Shanghai Municipal Science and Technology Commission (No.: 08JC1413600); Shanghai Committee of Science and Technology (11DZ2260200); and 985 Tumor Joint Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.