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Chunk #3 — Review — Assays for genome-wide chromatin accessibility — General considerations

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Chromatin accessibility: a window into the genome.
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Chromatin accessibility approaches measure directly the effect of chromatin structure modifications on gene transcription, in contrast to histone chromatin immunoprecipitation with NGS (ChIP-seq) (for a thorough review on ChIP-seq read [31–33]) where such effects must be inferred by presence or absence of overlapping histone tail modifications. Also, chromatin accessibility assays do not require antibodies or epitope tags that can introduce potential bias. An important limitation with all chromatin accessibility experiments is the lack of a standard for the number of replicates required to achieve accurate and reproducible results. This is because replicate number depends on the achieved signal-to-noise ratio, which can vary depending on the assay used, the assay conditions, and the cell or tissue type. In addition, replicate number is a function of technical variance, which is also experiment-specific and difficult to model in a generalized format. Following we discuss chromatin accessibility assays that directly (DNase-seq, FAIRE-seq and ATAC-seq) isolate accessible locations of a genome separate from MNase-seq, which indirectly evaluates chromatin accessibility, and present their principal mode of action, examples of application and main experimental considerations (Table 1).Table