Roles of biotinylation of histones in chromatin structure

GABRIELA CAMPOREALE, NAGARAMA KOTHAPALLI, GAUTAM SARATH, JANOS ZEMPLENI

Nutrients and Cell Signaling

Taylor and Francis Group

Lugar: Boca Raton, Fl - EEUU; Año: 2005; p. 277 - 295

The major components of chromatin are (i) DNA; (ii) a group of proteins named histones; and (iii) various non-histone proteins. Folding of DNA into chromatin is mediated primarily by histones (1). Five major classes of histones have been identified inmammals: H1, H2A, H2B, H3, and H4. Histones are small proteins (11 to 22 kDa)consisting of a globular domain and a more flexible and charged amino terminus (histone "tail"). Lysine and arginine residues account for a combined >20% of all amino acid residues in histones, causing the basic properties of these proteins.DNA and histones form repetitive nucleoprotein units, the nucleosomes. Each nucleosome ("nucleosome core particle") consists of 146 basepairs of DNA wrapped around an octamer of core histones (one H3-H3-H4-H4 tetramer and two H2A-H2B dimers). The binding of DNA to histones is of electrostatic nature, and is mediated by the association of negatively charged phosphate groups of DNA with positively charged ε-amino groups (lysine moieties) and guanidino groups (arginine moieties) of histones. The amino terminal tail of histones protrudes from the nucleosomes; covalent modifications of this tail affect the structure of chromatin and form the basis for gene regulation, replication, and DNA repair as described below. The DNA located between nucleosome core particles is called linker DNA and is associated with histone H1. Histone tails are modified by covalent acetylation, methylation, phosphorylation, ubiquitination, and poly (ADP-ribosylation) of ε-amino groups (lysine), guanidino groups (arginine), and hydroxyl groups (serine). These modifications of histone tails ("histone code") may considerably extend the information potential of the DNA code and gene regulation, given that the enzymes catalyzing these modifications are specific for amino acid residues. Multiple signaling pathways converge on histones to mediate covalent modifications of these proteins. For example, binding of nuclear receptors to DNA may recruit histone acetyl transferases to chromatin, leading to acetylation of histone tails. Modifications of histone tails may affect binding of chromatin-associated proteins, triggering cascades of downstream histone modifications. For example, it has been proposed that methylation of arginine-3 in histone H4 recruits the histone acetyl transferase Esa1 to yeast chromatin, leading to acetylation of lysine-5 in histone H4. Histone modifications can influence each other in synergistic or antagonistic ways, mediating gene regulation. For example, phosphorylation of serine-10 inhibits methylation of lysine-9 in histone H3, but is coupled with lysine-9 and/or lysine-14 acetylation during mitogenic stimulation in mammalian cells. Conversely, deacetylation of lysine-14 in histone H3 is required to facilitate subsequent methylation of lysine-9, leading to transcriptional silencing. Ultimately, modifications of histones impact the access of enzymes such as RNA polymerases and DNA repair enzymes to DNA. Covalent modifications of histones are reversible, i.e., acetate moieties can be removed by histone deacetylases, and phosphates can be removed by phosphatases. The mechanism leading to removal of methyl groups is uncertain. It has been proposed that methylation marks are removed by proteolytic processing of histones, i.e., the methylated histone tail is clipped off. It is uncertain whether ubiquitination of histones plays a role in this process.