Holocarboxylase synthetase interacts physically with the nuclear receptor corepressor, histone deacetylase 1, and a novel splicing variant of histone deacteylase 1 to repress repeats

Holocarboxylase synthetase (HLCS) is a nuclear protein that catalyzes the binding of biotin to distinct lysine residues in chromatin proteins. HLCS-dependent epigenetic marks are overrepresented 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. Here we tested the hypothesis that HLCS interacts physically with nuclear receptor corepressor (N-CoR) and histone deacetylase 1 (HDAC1), thereby contributing toward the removal of lysine-9 acetylated histone H3 (H3K9ac) 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 long terminal repeats (LTRs) 15 and 22, respectively, in human embryonic kidney HEK293 cells compared with 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 toward the transcriptional repression of repeats, presumably increasing genome stability.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Gene Source Type: research