In the nuclei of eukaryotic cells, DNA wraps around the octamer of histone proteins to form the nucleosome, in a structure like ‘beads on a string’, which makes up the basic unit of chromatin. Chromatin further folds into higherlevel structures, loosely or tightly, which helps to determine the accessibility of the DNA. For instance, actively transcribed regions tend to be in looser chromatin structures so that transcription factors and RNA polymerases can access the genes. Chromatin structure can be altered by various post-translational modifications of the N-terminal tail residues of histone proteins. For example, acetylation of a lysine residue can neutralize its positive charge and weaken the binding between the histone and the negatively charged DNA, which exposes the DNA to regulatory proteins. Methylation is another common type of histone modification; for example, the lysine at the fourth position of the H3 histone can be mono-, di-or tri-methylated (denoted as H3K4me1, H3K4me2 and H3K4me3, respectively).

By examining histone modification patterns at highly conserved noncoding regions in mouse embryonic stem cells, Bernstein et al. found ‘bivalent domains’ of histone modifications (ie, harboring both the repressive mark H3K27me3 and the active mark H3K4me3) near genes with poised transcription [1]. When embryonic stem cells differentiate into more specialized cells (eg, neural precursor cells), a subset of the bivalent domains are resolved (ie, H3K27me3 becomes weaker, while H3K4me3 becomes stronger, and these loci coincide with genes that are actively transcribed in neural precursor cells). Thus, combinations of histone marks are indicative of transcriptional states.