Roke Iko Biology 3371 September 13, 2010 Nucleosome Positioning and its Effect on Gene Expression DNA

utilizes transcription factors which are proteins that control transcription from DNA to mRNA. Each transcription factor binds to a specific recognition sequence/ aided by DNAbinding domains. Recognition sequences occur repeatedly on DNA and thus in theory TFs should bind to any sequence that is recognized. However the presence of a recognition sequence does not automatically mean that a recognition site is present. If the sequence is not a site, the TFs will not bind and gene expression will fail. One very important factor that determines whether TFs will function is the presence of nucleosomes. Segal et al propose that there is a relationship between nucleosome presence, TF binding sites, and TFS. Both nucleosomes and transcription factors can bind to TF binding sites; this is attributed to the fact that nucleosomes can bind almost anywhere on DNA. However, regions with active TF binding sites are usually nucleosome depleted while sites where nucleosomes do bind are inaccessible to transcription factors. In Figure 2, we notice that GAL4, a regulatory protein of yeast, binds to four sites on the chromosome. The binding sites of GAL4 are not blocked by any nucleosomes and thus are able to activate transcription of the GAL1 and GAL10 genes. The authors propose that nucleosome binding is directly responsible for TF binding and thus regulation of gene expression. Genomes regulate where binding proteins will attach by placing nucleosomes over nonfunctioning sites (777). Figure 4a shows a chart plotting average nucleosome occupancy vs genomic locations. Nucleosomes are abundant in areas like the

centromere and intergenic regions, but less than 70% occupancy in transfer RNA and telomeres. We can attribute this difference to the fact that fewer nucleosomes are in areas that are more transcribed. This data shows that nucleosome occupancy is higher in areas that areas that are not transcribed often and lower in areas that are more transcribed. Figure 4b depicts the relationship between nucleosome occupancy and functional sites; nucleosomes are strategically placed over non-functional TF sites to prevent binding. In figure 4c, the graph shows that most functional binding sites have lower nucleosome occupancy levels. Segals study brings evidence that nucleosome positioning is related to TF binding and that the genome encodes nucleosome positioning particularly over non-functional binding sites.