The Impact of Chromatin

Abstract

For reasons of simplicity schematic pictures of gene regulation often represent genomic DNA as a straight horizontal line. However, the diploid human genome of 2 × 3.26 billion bp, lines up to a length of 2 m. This is an architectural challenge for packing the genome into a nucleus of an approximately 200,000 times smaller diameter. The highly condensed packing of genomic DNA is achieved through:

• (i) wrapping it around nucleosomes,

• (ii) forming fibers of different diameter and

• (iii) chromatin loops.

Together with a number of non-histone proteins some 30 million nucleosomes per cell determine the accessibility to the genome sequence. This is the first and most important step in the decision, whether a gene can be transcribed. The density of chromatin packing can be considered as a kind of indexing, whether the information of a given genomic region can be used or not. This indexing changes during development. In stem cells a large proportion of the genes are accessible in open chromatin, whereas in terminally differentiated cells many genes that are not needed for determining the phenotype of the cells are hidden in closed chromatin.

The wrapping of genomic DNA around nucleosomes and the post-translational modification of histone tails by a set of chromatin modifying enzymes are the molecular events for determining the density of chromatin packing. Furthermore, large protein complexes that are formed by transcription factors, polymerases and other nuclear non-histone proteins organize the 3-dimensional architecture of the chromatin into functional units being used for most efficiently coordinated gene expression.

In this chapter, we will discuss the difference between eu- and heterochromatin and the transition between these chromatin states. We will understand the nucleosome as a functional chromatin subunit and will discuss the properties and modifications of histones forming these nucleosomes. This will provide the basis for a more detailed discussion of the histone code (Chap. 8), the epigenome (Chaps. 9 and 10), chromatin remodeling (Chap. 11) and nuclear architecture (Chap. 12).