Histone biotinylation is a naturally occurring phenomenon

Abstract

Modifications of histones such as methylation and acetylation are involved in gene regulation. We recently identified a diet‐dependent histone modification, biotinylation of lysines, mediated by holocarboxylase synthetase (HCS). HCS is a chromatin protein. Knockdown of HCS decreases histone biotinylation in human cells. We identified ten biotinylation sites in histones using histone‐based synthetic peptides and biotinylation site‐specific antibodies. A recent study (Healy et al., 2009) has questioned the occurrence of histone biotinylation in vivo. Here, we provide unambiguous evidence in support of histone biotinylation in a number of primary and transformed human cells. Our biotinylation site‐specific antibodies, unlike the commercial antibodies used by Healy, do not cross react with methylated and acetylated histones. We detected biotinylated histones in various cell lines using anti‐biotin, streptavidin, and target‐specific antibodies. Cells of the lymphoid lineage produced the strongest biotinylation signal, which might explain the failure to detect histone biotinylation in HeLa cells in Healy's studies. Current studies focus on detecting biotin in native histones using [3H]biotin, customized [14C]carbonyl‐labeled biotin, and mass spectrometry in Jurkat cells. (UNL ARD Hatch grant, NIH DK063945, DK077816, DK082476 and ES015206, USDA CSREES 2006‐35200‐17138, and NSF EPS 0701892.)