2003). Transposable elements are thought to have been important in the evolution of regulatory sequences and networks (Feschotte 2008). For example, a number of families of long terminal repeat elements (affili ated to class I endogenous retroviruses) were found to be enriched for binding sites for p53 (Wang et al. 2007). These represented a third of p53 binding sites in the human genome previously identified by genome-wide in vivo binding studies using chromatin immunoprecip-itation (ChIP) (Box 11.7) (Wei et al. 2006). Evolutionary analysis suggests dispersal by insertion and deletion of these long terminal repeat elements over 40 million years from a primate ancestor. This illustrates how a primate-specific regulatory network may arise with multiple genes controlled by a given transcription factor family, in this case the master regulatory factor p53 (Fig. 8.3) (Wang et al. 2007; Feschotte 2008).
Transposable elements may also result in novel functional sequences that are advantageous to the host (an example of exaptation or cooption), as illustrated by the origins of enhancers in SINE retrotransposons for the ISL1 and POMC genes (Box 8.2) (Bejerano et al. 2006; Santangelo et al. 2007). Transposable elements are thought to directly modulate gene expression in many different ways involving both transcriptional and post-transcriptional mechanisms (Fig. 8.4). As we will see during the course of this chapter the consequences of mobile DNA elements are diverse and can be profound, contributing to the birth of new genes through fusion events, or can have deleterious consequences, for example disrupting open reading frames (ORFs) or predisposing to homologous recombination, and can result in a range of disease phenotypes.
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