Table 1 Current genome-wide high-throughput chromatin accessibility assays

MNase-seq

Any cell type 1 to 10 million cells

Paired-end or Single-end

MNase digests unprotected DNA

Maps the total nucleosome population in a qualitative and quantitative manner

1. Requires many cells.

[37, 46, 49]

2. Laborious enzyme titrations.

3. Probes total nucleosomal population, not active regulatory regions only.

4. Degrades active regulatory regions, making their detection possible only indirectly.

5. Requires 150 to 200 million reads for standard accessibility studies of the human genome.

DNase-seq

Any cell type 1 to 10 million cells

Paired-end or Single-end

DNase I cuts within unprotected DNA

Maps open chromatin

1. Requires many cells.

[61, 75, 76]

2. Time-consuming and complicated sample preparations.

3. Laborious enzyme titrations.

4. Requires 20 to 50 million reads for standard accessibility studies of the human genome.

FAIRE-seq

Any cell type 100,000 to 10 million cells

Paired-end or Single-end

Based on the phenol-chloroform separation of nucleosome-bound and free sonicated areas of a genome, in the interphase and aqueous phase respectively

Maps open chromatin

1. Low signal-to-noise ratio, making computational data interpretation very difficult.

[86–90]

2. Results depend highly on fixation efficiency.

3. Requires 20 to 50 million reads for standard accessibility studies of the human genome.

ATAC-seq

500 to 50,000 freshly isolated cells

Paired-end

Unfixed nuclei are tagged in vitro with adapters for NGS by purified Tn5 transposase. Adapters are integrated into regions of accessible chromatin

Maps open chromatin, TF and nucleosome occupancy

1. Contamination of generated data with mitochondrial DNA.

[103]

2. Immature data analysis tools.

3. Requires 60 to 100 million reads for standard accessibility studies of the human genome.