Post-translational modification of histones by acetylation and methylation are frequent and important changes of chromatin that influence many biological processes in the context of development and cellular responses. The present understanding of the function of histone modifications is summarized in the histone code model.
There are two pairs of chromatin modifying enzymes, each with antagonizing activity: histone acetylases and deacetylases and histone methylases and demethylases. These proteins are components of larger protein complexes and are characterized by containing either bromodomains, chromodomains or PHD fingers as specific recognition motifs for chromatin modifications.
The genome-wide view on histone modifications and chromatin modifier locations extents the histone code model. This view indicates that chromatin modifiers of antagonizing activity often co-localize and fine-tune each other in the control of active, poised and silent genes. Several chromatin modifier proteins bind often together to common genomic loci. However, they can also vary in their association partners and therefore recognize also different genomic loci. Chromatin modifiers bind sets of genes with related functions. However, in comparison of different cell types, chromatin modifiers distribute to different loci but largely retain their modular associations.
The importance of appropriate maintainance of histone modification patterns is in particular emphasized by the fact that the dysregulation of histone methyltransferases and demethylases can lead to cancer and other diseases.
In this chapter, we will discuss the histone code model as the presently best explanation for the functional impact of post-translational histone modifications. In this context we will understand that chromatin modifiers are proteins that add (“write”), interpret (“read”) and/or remove (“erase”) histone modifications. The genome-wide view histone modifications and chromatin modifiers locations will widen our perspective on the impact of the histone code in health and disease.
KeywordsHistone code Post-translational histone modification Chromatin modifier Bromodomain, chromodomain PHD finger Histone methylation Histone acetylation Polycomb proteins Genome-wide analysis Active gene Primed gene Silent gene Cancer
- Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert J-P, Barsyte-Lovejoy D, Felletar I, Volkmer R, Müller S, Pawson T, Gingras A-C, Arrowsmith CH, Knapp S (2012) Histone recognition and large-scale structural analysis of the human Bromodomain family. Cell 149:214–231PubMedCrossRefGoogle Scholar
- Ram O, Goren A, Amit I, Shoresh N, Yosef N, Ernst J, Kellis M, Gymrek M, Issner R, Coyne M, Durham T, Zhang X, Donaghey J, Epstein CB, Regev A, Bernstein BE (2011) Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells. Cell 147:1628–1639PubMedCrossRefGoogle Scholar