Predictive chromatin signatures in the mammalian genome

Abstract

The DNA sequence of an organism is a blueprint of life: it harbors not only the information about proteins and other molecules produced in each cell, but also instructions on when and where such molecules are made. Chromatin, the structure of histone and DNA that has co-evolved with eukaryotic genome, also contains information that indicates the function and activity of the underlying DNA sequences. Such information exists in the form of covalent modifications to the histone proteins that comprise the nucleosome. Thanks to the development of high throughput technologies such as DNA microarrays and next generation DNA sequencing, we have begun to associate the various combinations of chromatin modification patterns with functional sequences in the human genome. Here, we review the rapid progress from descriptive observations of histone modification profiles to highly predictive models enabling use of chromatin signatures to enumerate novel functional sequences in mammalian genomes that have escaped previous detection.

Figure 1.

Modifications of histone H3. Lysine residues on histone H3 can be mono-, di- or tri-methylated. Shown are modifications H3K4me1, H3K4me3 and H3K36me3, which mark active/poised enhancers, active/poised promoters and actively transcribed regions, respectively. me, methylation.

Figure 2.

Chromatin signatures and gene expression. The promoters of both actively expressed and unexpressed genes are marked by H3K4me3. In contrast, only actively expressed genes have exons marked by H3K36me3 and nearby enhancers marked by H3K4me1.

Figure 3.

Identifying chromatin signatures with ChromaSig. (Top) A snapshot of histone methylations, CTCF and RNA polymerase II mapped using ChIP-Seq in CD4+ T cells (10). White bars indicate no enrichment, whereas black bars indicate enrichment. (Bottom) Frequently occurring chromatin signatures found by ChromaSig in examining genome-wide maps of histone methylations.