Histone H3 Amino-Terminal Tail Phosphorylation and Acetylation: Synergistic or Independent Transcriptional Regulatory Marks?

Eukaryotic cells package their large genomes intohigher-order nucleoprotein complexes termed chromatin,creating a barrier to many nuclear processes that requireaccess to the DNA. The fundamental unit of chromatin isthe nucleosome, which consists of an octamer of core histone proteins (two each of histone H2A, H2B, H3, andH4). Each histone octamer contains an (H3-H4)2 tetramerflanked by two H2A-H2B dimers that form a nucleosomecore that binds to and wraps 1.65 turns (147 bp) of superhelical DNA (Luger et al. 1997). This wrapping of DNAaround the nucleosome core partially restricts access toDNA-binding proteins. In addition, histone proteins alsocontain nonstructured amino- and carboxy-terminal taildomains that protrude from the nucleosome core and mayinteract with neighboring nucleosomes and nucleosomalDNA to further restrict access to DNA-binding proteins.Individual nucleosomes are connected by 10–60 bp of"linker" DNA to form contiguous nucleosomal arraysthat are condensed into highly compacted 100–400-nmthick fibers in interphase chromosomes. Chromosomesare further compacted during mitosis, condensing theDNA up to 10,000-fold (Hayes and Hansen 2001; Woodcock and Dimitrov 2001). How then do cells regulate theaccessibility of their genomic DNA...