Epigenetic regulation of chromatin structure and gene function by biotin: are biotin requirements being met?

Abstract

Histones H2A, H3, and H4 are modified by covalent binding of the vitamin biotin to distinct lysine residues. Binding of biotin to histones is mediated by holocarboxylase synthetase (HCS) and perhaps biotinidase. Biotinylation of lysine-12 in histone H4 (K12BioH4) plays roles in gene repression, stability of repeat regions and transposable elements, and regulation of biotin transporter expression in eukaryotes. Decreased biotinylation of histones in biotin-deficient and HCS-deficient human cells and Drosophila melanogaster impairs stress resistance, life span, and biotin homeostasis. Chromatin is comprised of DNA and DNA-binding proteins, i.e., histones and non-histone proteins. Histones play a predominant role in the folding of DNA into chromatin.1 Five major classes of histones have been identified in mammals: H1, H2A, H2B, H3, and H4. Histones consist of a globular domain and a more flexible amino terminus (histone “tail”). DNA and histones form repetitive nucleoprotein units, the nucleosomes.1 Each nucleosome (“nucleosomal core particle”) consists of 146 base pairs of DNA wrapped around an octamer of core histones (one H3-H3-H4-H4 tetramer and two H2A-H2B dimers). The amino terminal tail of histones protrudes from the nucleosomal surface; covalent modifications of this tail affect the structure of chromatin and form the basis for gene regulation.1–3 Amino acid residues in histone …