Holocarboxylase synthetase interacts physically with nuclear receptor co-repressor, histone deacetylase 1 and a novel splicing variant of histone deacetylase 1 to repress repeats
Copyright policy )Holocarboxylase synthetase interacts physically with nuclear receptor co-repressor, histone deacetylase 1 and a novel splicing variant of histone deacetylase 1 to repress repeats
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 (Lys9-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.
- University of Nebraska System United States
Models, Molecular, Genetic Complementation Test, Acetylation, Histone Deacetylase 1, Epigenetic Repression, Peptide Fragments, Recombinant Proteins, Histones, Alternative Splicing, HEK293 Cells, Amino Acid Substitution, Proteolysis, Humans, Immunoprecipitation, Nuclear Receptor Co-Repressor 1, Carbon-Nitrogen Ligases, Mutant Proteins, Protein Interaction Domains and Motifs, Protein Processing, Post-Translational, Biomarkers
Models, Molecular, Genetic Complementation Test, Acetylation, Histone Deacetylase 1, Epigenetic Repression, Peptide Fragments, Recombinant Proteins, Histones, Alternative Splicing, HEK293 Cells, Amino Acid Substitution, Proteolysis, Humans, Immunoprecipitation, Nuclear Receptor Co-Repressor 1, Carbon-Nitrogen Ligases, Mutant Proteins, Protein Interaction Domains and Motifs, Protein Processing, Post-Translational, Biomarkers
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