Abstract
Classically, HLCS is considered a protein biotinyl ligase. Evidence is emerging that HLCS also is a member of amultiprotein gene repression complex in human chromatin that mediates epigenetic synergies between biotinylation andmethylation events. Here we tested that HLCS also integratesgene expression by histone deacetylation, and that this effect is mediated by physical interactions among HLCS, N‐CoR, and HDACs. Physical interactions between HLCS and HDAC1 were confirmed by three independent procedures, namely co‐immunoprecipitation (co‐IP), limited proteolysis assays (LPA), and yeast two‐hybrid assays (Y2H). In addition, we developed a protocol to predict HLCS‐binding proteins in silico. Using this protocol, we predict that HLCS also interacts with N‐CoR. Studies of HLCS/N‐CoR interactions by co‐IP, LPA, and Y2H are currently in progress. We conclude that we discovered a novel epigenetic mechanism by which HLCS represses genes. Supported by ARD Hatch, and NIH DK063945, DK077816, and DK082476.
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