Increased Euchromatin formation Histone acetylation promotes Euchromatin formation (transcriptionally active DNA). Deacetylation and methylation promotes Heterochromatin formation (transcriptionally inactive DNA). There are five classes of histones, designated HI, H2A, H2B, H3, and H4. These small proteins are positively charged at physiologic pH as a result of their high content of lysine and arginine. Because of their positive charge, they form ionic bonds with negatively charged DNA. Histones help in condensation of DNA into chromosomes. Two molecules each of H2A, H2B, H3, and H4 form the structural core of the individual nucleosome "beads." Around which a segment of the DNA double helix is wound nearly twice. (Histone HI, is not found in the nucleosome core, but instead binds to the linker DNA chain between the nucleosome beads.). Nucleosomes are fuher arranged into increasingly more complex structures that organize and condense the long DNA molecules into chromosomes. These histone proteins can undergo reversible modifications at their N-terminal end (like acetylation, methylation or phosphorylation). These modifications help in regulation of gene expression. Acetylation of the lysine residues at the N terminus of histone proteins removes positive charge on the lysine and thereby decreases the interaction of the histone with the negatively charged DNA. As a result, the condensed chromatin is transformed into a more relaxed structure allowing transcription factors to access specific regions on the DNA. Deacetylation restores the positive charge, causing stronger interactions between histones and DNA. Thus histone acetylation enhances transcription while histone deacetylation represses transcription. Relaxed, transcriptionally active DNA is referred to as euchromatin. More condensed, inactive DNA is referred to as heterochromatin. Histone acetylation is catalyzed by histone acetyltransferases (HATS) and histone deacetylation is catalyzed by histone deacetylases (denoted by HDs or HDACs). Another difference noted between transcriptionally active and inactive chromatin is the extent of methylation of cytosine bases in CG-rich regions (CG islands) of many genes. It has been observed that transcriptionally active genes are less methylated (hypomethylated) than their inactive counterpas. Thus formation of euchromatin is promoted by acetylationand formation of heterochromatin is promoted by deacetylation and methylation. The action of methylation is indirect and has no effect upon charge.