SUMO promotes HDAC-mediated transcriptional repression

Mol Cell. 2004 Feb 27;13(4):611-7. doi: 10.1016/s1097-2765(04)00060-7.

Abstract

Recently, SUMO modification has been shown to impart repressive properties on several transcriptional regulatory proteins. Indeed, the ETS domain transcription factor Elk-1 is modified by SUMO, and this modification is reversed by ERK MAP kinase pathway activation. This causes a switch from a repressive to activated state. However, the mechanism(s) of SUMO-mediated transcriptional repression is unclear. Here, we have investigated how sumoylation of Elk-1 leads to transcriptional repression. We demonstrate that sumoylation of Elk-1 results in the recruitment of histone deacetylase activity to promoters. In particular, our data point to a key role for HDAC-2. This recruitment leads to decreased histone acetylation and hence transcriptional repression at Elk-1 target genes. Thus, our data demonstrate an important integration point for two protein-modifying pathways in the cell, the SUMO and deacetylation pathways, that combine to promote transcriptional repression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • DNA-Binding Proteins*
  • Genes, Reporter
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Histone Deacetylases / metabolism*
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / chemistry
  • RNA, Small Interfering / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • SUMO-1 Protein / genetics*
  • SUMO-1 Protein / metabolism
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transcriptional Activation
  • ets-Domain Protein Elk-1

Substances

  • DNA-Binding Proteins
  • ELK1 protein, human
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • SUMO-1 Protein
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • Glutathione Transferase
  • Mitogen-Activated Protein Kinases
  • Histone Deacetylases