Holocarboxylase synthetase interacts physically with nuclear receptor co-repressor, histone deacetylase 1 and a novel splicing variant of histone deacetylase 1 to repress repeats

Dandan Liu, Janos Zempleni

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

HLCS (holocarboxylase synthetase) is a nuclear protein that catalyses the binding of biotin to distinct lysine residues in chromatin proteins. HLCS-dependent epigenetic marks are over-represented in repressed genomic loci, particularly in repeats. Evidence is mounting that HLCS is a member of a multi-protein gene repression complex, which determines its localization in chromatin. In the present study we tested the hypothesis that HLCS interacts physically with N-CoR (nuclear receptor co-repressor) and HDAC1 (histone deacetylase 1), thereby contributing toward the removal of H3K9ac (Lys 9-acetylated histone H3) gene activation marks and the repression of repeats. Physical interactions between HLCS and N-CoR, HDAC1 and a novel splicing variant of HDAC1 were confirmed by co-immunoprecipitation, limited proteolysis and split luciferase complementation assays. When HLCS was overexpressed, the abundance of H3K9ac marks decreased by 50% and 68% in LTRs (long terminal repeats) 15 and 22 respectively in HEK (human embryonic kidney)-293 cells compared with the controls. This loss of H3K9ac marks was linked with an 83% decrease in mRNA coding for LTRs. Similar patterns were seen in pericentromeric alpha satellite repeats in chromosomes 1 and 4. We conclude that interactions of HLCS with N-CoR and HDACs contribute towards the transcriptional repression of repeats, presumably increasing genome stability.

Original languageEnglish (US)
Pages (from-to)477-486
Number of pages10
JournalBiochemical Journal
Volume461
Issue number3
DOIs
StatePublished - Aug 1 2014

Keywords

  • Chromatin
  • Epigenetics
  • Gene repression
  • Histone deacetylase 1 (HDAC1)
  • Holocarboxylase synthetase (HLCS)
  • Nuclear receptor co-repressor (N-CoR)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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