Chromatin landscape: methylation beyond transcription

Abstract

The nucleus is organized and compartmentalized into a highly ordered structure that contains DNA, RNA, chromosomal and histone proteins. The dynamics associated with these various components are responsible for making sure that the DNA is properly duplicated, genes are properly transcribed, and the genome is stabilized. It is no surprise that alterations in these various components are directly associated with pathologies like cancer. This Point of View focuses on the role the chromatin modification landscape, especially histone 3 lysine 9 methylation (H3K9me), and heterochromatin proteins (HP1) play in regulating DNA-templated processes, with a particular focus on their role at non-genic regions and effects on chromatin structure. These observations will be further extended to the role that alterations in chromatin landscape will contribute to diseases. This Point of View emphasizes that alterations in histone modification landscapes are not only relevant to transcription but have broad range implications in chromatin structure, nuclear architecture, cell cycle, genome stability and disease progression.

Figure 1

Enzymes controlling histone methylation dynamics and chromosomal domains of histone methylation. Lysines are mono-, di- and trimethylated by multiple histone methyltransferases (KMT). The different KMT are shown in the left-most part. The histone lysine demethylases (KDM) remove methyl groups from the lysines. The different KDMs that have been discovered are in the left part adjacent to the reactions. The sites the KMTs and KDMs modify are indicated next to their names. The degree of methylation these enzymes impact is based on their clustering (see color box code: blue, methylate from unmodified to trimethylated; green, unmodified to dimethylated; brown, monomethylation to trimethylation; black, only function at the indicated modification sate). The methyltransferases with an * indicate the last reaction is not as strong. The right part summarizes localization data indicating the relationship of each modification to active open reading frames, as well as particular chromosomal domains. For open reading frames: ORF, open reading frame; TSS, transcriptional start site; UTR, untranslated region; NC, no correlation to open reading frame; NA, not on active genes and ND, not determined. For chromosomal domains: T, telomere; ST, subtelomere; C, centromere; PC, perictromeric; GD, gene deserts; RD, repetitive regions and LAD, lamin associated domains. Data on chromosomal domains of modifications was compiled from references , , and . We apologize to all those whose work is summarized in this figure that we were unable to cite due to space limitations.