K12 biotinylated histone H4 is enriched at human endogenous retrovirus promoter regions and may function in retroviral silencing

The human genome contains numerous endogenous retroviral (HERV) elements (~8%) some of which have been associated with various disease states, including cancer. Most HERVs are resided in the human genome as solitary long terminal repeats (LTRs), but some also contain viral open reading frames. Silencing LTR elements is important to prevent inappropriate transcriptional activation or repression, and to block retrotransposition which would lead to genomic instability. Our laboratory has identified that biotinylation of lysine 12 in histone H4 (K12Bio H4) mediated by holocarbocylase synthetase (HCS) could represent a novel epigenetic silencing mechanism. Here, we investigated the effect of culturing human Jurkat lymphoid cells in medium containing 0.025 nmol/L, 0.25 nmol/L, and 10 nmol/L biotin (deficient, physiological, and pharmacological concentrations) on de‐repression of HERV silencing. The relative enrichment of K12Bio H4 at HERV promoters was quantified by using chromatin immunoprecipitation assays (ChIP) followed by amplification of HERV LTR sequences. Our data indicates a 1.4‐fold enrichment in samples from cultures at 10nM biotin compared with cultures at 0.25 nM biotin, and 2‐fold enrichment versus identical cultures undergoing HCS knock‐down through RNAi. Our data provide preliminary evidence that biotinylation of K12 in H4 may participate in silencing HERVs.