We can get some idea of the prevalence of epigenetic changes by comparing identical twins. Their genomes have the same sequence of nucleotides, and, obviously, many features of identical twins—such as their appearance—are strongly determined by the genome sequences they inherit. When their gene expression, histone modification, and DNA methylation patterns are compared, however, many differences are observed. Because these differences are roughly correlated not only with age but also with the time that the twins have spent apart from each other, it has been proposed that some of these differences are heritable from cell to cell and are the result of environmental factors. Although these studies are in early stages, the idea that environmental events can be permanently registered as epigenetic changes in our cells is a fascinating one that presents an important challenge to the next generation of biological scientists.
Figure 7–52 Mammalian X-chromosome inactivation. X-chromosome inactivation begins with the synthesis of Xist (X-inactivation specific transcript) rnA from the XiC (X-inactivation center) locus and moves outward to the chromosome ends. According to the model depicted here, the long (≈20,000 nucleotides) Xist rnA has many low-affinity binding sites for the structural components of chromosomes and spreads by releasing its hold on one portion of the chromosome while grasping another. the continued synthesis of Xist from the center of the chromosome drives it to the ends. As shown, Xist rnA does not move linearly along the chromosomal DnA, but, instead, moves first across the base of chromosome loops. it has been proposed that the portions of chromosomal DnA at the tips of long loops contain the 10% of genes that escape X-chromosome inactivation.
Eukaryotic cells can use inherited forms of DNA methylation and inherited states of chromatin condensation as additional mechanisms for generating cell memory of gene expression patterns. An especially dramatic case that involves chromatin condensation is the inactivation of an entire X chromosome in female mammals. DNA methylation underlies the phenomenon in mammals of genomic imprinting, in which the expression of a gene depends on whether it was inherited from the mother or the father.
In principle, every step required for the process of gene expression can be controlled. Indeed, one can find examples of each type of regulation, and many genes are regulated by multiple mechanisms. As we have seen, controls on the initiation of gene transcription are a critical form of regulation for all genes. But other controls can act later in the pathway from DNA to protein to modulate the amount of gene product that is made—and in some cases, to determine the exact amino acid sequence of the protein product. These post-transcriptional controls, which operate after RNA polymerase has bound to the gene’s promoter and has begun RNA synthesis, are crucial for the regulation of many genes.
In the following sections, we consider the varieties of post-transcriptional regulation in temporal order, according to the sequence of events that an RNA molecule might experience after its transcription has begun (Figure 7–54).
Figure 7–53 Four distinct mechanisms that can produce an epigenetic form of inheritance in an organism.
(A) epigenetic mechanisms that act in cis. As discussed in this chapter, a maintenance methylase can propagate specific patterns of cytosine methylation (see figure 7–44). As discussed in Chapter 4, a histone modifying enzyme that replicates the same modification that attracts it to chromatin can result in the modification being self-propagating (see figure 4–44). (B) epigenetic mechanisms that act in trans. positive feedback loops, formed by transcriptional regulators are found in all species and are probably the most common form of cell memory. As discussed in Chapter 3, some proteins can form self-propagating prions (figure 3–33). if these proteins are involved in gene expression, they can transmit patterns of gene expression to daughter cells.