The nucleosome is comprised of an octamer histone core wrapped nearly 1.7 times by approximately 147 bp of DNA that represents the basic unit of eukaryotic chromatin. While packaging of nucleosomes into a higher order structure enables the compaction of chromatin into the nucleus, it also limits access to various DNA binding factors, thereby placing an accessibility constraint on all DNA-dependent processes. Nucleosome arrangements on genomic DNA are defined both in terms of positioning and occupancy. In particular, nucleosome positioning and occupancy at transcription start sites is thought to impact gene expression. Accordingly, genome-wide nucleosome mapping studies in yeast have revealed a nucleosome-depleted region upstream of most TSSs that likely permits access by the transcription machinery. However, some yeast promoters appear to be occupied by nucleosomes that are actively removed in response to inducing signals. Such promoters display higher transcriptional plasticity and are more responsive to signaling pathways, than are promoters with pronounced NDRs, suggesting that nucleosome positioning represents a mechanism to achieve regulated gene expression in yeast. Nucleosome positioning may play an even greater role in the regulation of gene expression in metazoans since Butenafine hydrochloride regulatory DNA sequences are invariant among all cells of a multi-cellular organism, but only a subset of cells may express a specific gene. Indeed, while many promoters in flies, worms, fish, and Tulathromycin B humans display NDRs upstream of TSSs, many other promoters are occupied by nucleosomes and inductive signals cause nucleosome rearrangements at such promoters. This suggests that nucleosomes need to be rearranged at many metazoan promoters prior to transcription and, accordingly, there is an overall bias towards expressed promoters having a more pronounced NDR. Nucleosome positioning is partially encoded by the DNA sequence and experimental studies have identified sequences that favor or disfavor nucleosome binding. More recently, experimentally derived nucleosome position information has been used to design theoretical models for the purpose of predicting nucleosome positioning de novo. These models are reasonably successful at predicting nucleosome positions in yeast, but are less successful in C. elegans or in human cells. In particular, the models appear less accurate at predicting nucleosome positioning at metazoan regulatory regions. Notably, regulatory regions have higher G+C content in metazoans than in yeast and are therefore more likely to be bound by nucleosomes. As discussed above, such nucleosomes are actively removed in cells where the corresponding promoter is expressed, possibly accounting for the observed discrepancies between predicted and actual nucleosome positioning. Nucleosomes may be repositioned from such G+C rich promoter regions by a variety of mechanisms, including competition with sequence-specific transcription factors or the RNA Polymerase II complex, as well as by the action of ATP-dependent nucleosome remodelers. It is also worth noting that regions defined as NDRs are not necessarily completely devoid of nucleosomes, but may represent sites with less robust nucleosomes, perhaps because they contain histone variants such as H2.AZ or H3.3 that are less stably bound to DNA. Such nucleosomes are more easily displaced and might therefore make promoters more responsive to inductive signals, but would also make them more sensitive to DNase-based methods used to map nucleosome organization. Taken together, work to date suggests that active processes control nucleosome positioning at many promoters and that this is an important regulatory mechanism for inducible and cell-specific gene expression in metazoans.