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

Christian B. Gocke, Hongtao Yu

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere3255
JournalPLoS One
Volume3
Issue number9
DOIs
StatePublished - Sep 22 2008

Fingerprint

zinc finger motif
Zinc Fingers
Chromatin
modifiers (genes)
chromatin
Zinc
Histone Code
ubiquitin
transcription factors
Ubiquitin
Genes
Transcription
histones
Histones
Proteins
transcription (genetics)
promoter regions
Sumoylation
Co-Repressor Proteins
Tandem Repeat Sequences

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers. / Gocke, Christian B.; Yu, Hongtao.

In: PLoS One, Vol. 3, No. 9, e3255, 22.09.2008.

Research output: Contribution to journalArticle

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