Chromatin as a potential carrier of heritable information

Abstract

Organisms with the same genome can inherit information in addition to that encoded in the DNA sequence-this is known as epigenetic inheritance. Epigenetic inheritance is responsible for many of the phenotypic differences between different cell types in multicellular organisms. Work by many investigators over the past decades has suggested that a great deal of epigenetic information might be carried in the pattern of post-translational modifications of the histone proteins, although this is not as well established as many believe. For example, it is unclear whether and how the histones, which are displaced from the chromosome during passage of the replication fork and are often exchanged from the DNA template at other times, carry information from one cellular generation to the next. Here, we briefly review the evidence that some chromatin states are indeed heritable, and then focus on the mechanistic challenges that remain in order to understand how this inheritance can be achieved.

Figure 1

Processes likely to tune the precision of inheritance of chromatin states. For all figures, green and red circles represent histones in different modification states, while gray represents free nucleosomes drawn from the nucleoplasmic pool. (a) Dispersal of old nucleosomes determines the precision of chromatin inheritance. Examples show two distinct dispersal patterns, using red histones to indicate a potentially heritable modification. If histones displaced by the replication machinery rapidly reassociate with the chromosome following DNA synthesis, then short domains of a given histone modification state will be heritable (left), while slow reassociation will result in spreading and dilution of the old histones in a particular state (right). (b, c) Two models for feedback from old nucleosomes to new. In (b), new nucleosomes are modified by histone modifying enzymes recruited locally by old nucleosomes. In (c), green represents acetylated nucleosomes and red represents poorly acetylated nucleosomes. Regions of the genome associated with highly acetylated nucleosomes are replicated early in S phase, concordant with the acetylation of newly synthesized histones. Late in S phase, hypoacetylated chromatin is replicated, and new histones recruited to those regions are deacetylated. These models may be distinguished based on how small domains of histone modification behave during S phase.