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ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers.

Histone modifications in chromatin regulate gene expression. A transcriptional co-repressor complex containing LSD1-CoREST-HDAC1 (termed LCH hereafter for simplicity) represses transcription by coordinately removing histone modifications associated with transcriptional activation. RE1-silencing transcription factor (REST) recruits LCH to the promoters of neuron-specific genes, thereby silencing their transcription in non-neuronal tissues. ZNF198 is a member of a family of MYM-type zinc finger proteins that associate with LCH. Here, we show that ZNF198-like proteins are required for the repression of E-cadherin (a gene known to be repressed by LSD1), but not REST-responsive genes. ZNF198 binds preferentially to the intact LCH ternary complex, but not its individual subunits. ZNF198- and REST-binding to the LCH complex are mutually exclusive. ZNF198 associates with chromatin independently of LCH. Furthermore, modification of HDAC1 by small ubiquitin-like modifier (SUMO) in vitro weakens its interaction with CoREST whereas sumoylation of HDAC1 stimulates its binding to ZNF198. Finally, we mapped the LCH- and HDAC1-SUMO-binding domains of ZNF198 to tandem repeats of MYM-type zinc fingers. Therefore, our results suggest that ZNF198, through its multiple protein-protein interaction interfaces, helps to maintain the intact LCH complex on specific, non-REST-responsive promoters and may also prevent SUMO-dependent dissociation of HDAC1.

Pubmed ID: 18806873

Authors

  • Gocke CB
  • Yu H

Journal

PloS one

Publication Data

September 22, 2008

Associated Grants

  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Cadherins
  • Chromatin
  • DNA-Binding Proteins
  • Gene Expression Regulation
  • HeLa Cells
  • Histone Deacetylase 1
  • Histone Deacetylases
  • Histone Demethylases
  • Histones
  • Humans
  • Nerve Tissue Proteins
  • Oxidoreductases, N-Demethylating
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Interaction Mapping
  • Repressor Proteins
  • Transcription Factors
  • Transcriptional Activation
  • Zinc Fingers