Chromatin Modifiers

Abstract

Post-translational modification of histone proteins by acetylation and methylation are frequent and important changes of chromatin. These epigenetic changes control many biological processes, such as cellular differentiation in the context of embryogenesis. 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, such as histone acetylases and deacetylases and histone methyltransferases and demethylases. These proteins are components of larger protein complexes and are characterized contain either bromodomains, chromodomains or PHD fingers as specific recognition motifs for chromatin modifications.

The genome-wide view on histone modifications and chromatin modifier locations extends the histone code model. This view indicates that chromatin modifiers of antagonizing activity frequently co-localize to common genomic loci and fine-tune each other in the control of active, poised and silent genes. However, they can also vary in their association partners and therefore recognize different genomic loci. Chromatin modifiers bind sets of genes with related functions and largely retain their modular associations, when they distribute to different genomic loci. The importance of appropriate maintenance of histone modification patterns is in particular emphasized by the fact that the dys-regulation 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 adding (“write”), interpreting (“read”) and/or removing (“erase”) histone modifications. The genome-wide view of histone modifications and chromatin modifier locations will widen our perspective on the impact of the histone code in health and disease.