Table 1.
DNA sequencing-based methods for mapping nucleosomes and/or chromatin accessibility.
| Assay | Description | References |
|---|---|---|
| MPE-seq | Radical-based linker DNA cleavage method that maps nucleosomal and sub-nucleosomal protected DNA fragments with minimal sequence bias [2]. | Ishii et al. 2015 |
| KAS-seq | Genome-wide mapping of ssDNA produced by transcriptionally active RNA polymerases. Compatible with low cell number [3]. | Wu et al. 2020 |
| FAIRE-seq | Non-nuclease genome-wide accessibility assay that uses formaldehyde fixation and sonication to enrich for hyper-accessible regions [4,5]. | Nagy et al. 2003 Giresi et al. 2007 |
| DNase-seq | Maps accessible regions of the genome with a bias toward hyper-accessible regions, e.g. enhancers and promoters [6]. | Boyle et al. 2008 |
| MNase-seq | Can map either hyper-accessible regions or nucleosome positions depending on enzyme dosage. MNase has strong cleavage bias based on base pair composition [7]. | Albert et al. 2007 |
| MACC | MNase accessibility metric determined by combining high MNase and low MNase measurements [8]. | Mieczkowski et al. 2016 |
| q-MNase | Similar to MACC, it uses titration of MNase, but also incorporates spike-in controls in experiment and analyses [9]. | Chereji et al. 2019 |
| MNase-SSP | Uses a single-stranded DNA library prep to map MNase-digested fragments. This method greatly lessens the base composition cleavage bias of standard double-stranded preps, and also efficiently captures sub-nucleosome-sized fragments [10]. | Ramani et al. 2019 |
| Array-seq | Long-read sequencing of partially digested chromatin by MNase. Main feature of interrogation is nucleosome phasing [11,12]. | Baldi et al. 2018 |
| ATAC-seq | Maps hyper-accessible regions using Tn5 transposase, which cuts and inserts sequencing adapters into cellular DNA in a single step. Compatible with single-cell protocols [13]. | Buenrostro et al. 2013 Buenrostro et al. 2018 |
| NA-seq | DNA accessibility measured by restriction enzyme and sequencing. Can probe hyper-accessible and other regions of the genome in the same assay. Resolution is dependent on number of restriction sites in the genome [14]. | Gargiulo et al. 2009 |
| RED-seq | Derivative of NA-seq that is performed on permeabilized cells and has an updated library prep workflow [15]. | Chen et al. 2014 |
| qDA-seq | Similar to NA-seq and RED-seq. Restriction enzymes are titrated to measure both initial cut rate and absolute accessibility [16]. | Chereji et al. 2019 |
| ORE-seq | Equivalent to qDA-seq. Cross-verified results with ODM-seq [17]. | Oberbeckmann et al. 2019 |
| ODM-seq | Methyltransferase accessibility assay. Nuclei are treated with M.SssI and M.CviPI followed by bisulfite-seq to measure cytosine methylation (5mC). Accessibility measurements were cross-verified with ORE-seq [18]. | Elisa Oberbeckmann et al. 2019 |
| DamID | Genetically encoded DNA adenine methyltransferase domain fused to an endogenous protein or by itself is expressed in living cells and modifies GATC sequences, which are detected by bisulfite-seq. Resolution of assay is limited by its cognate GATC site [19,20]. | van Steenlsel and Henikoff 2000 Sha et al. 2010 |
| NOMe-seq, MAPit-patch | Methyltransferase-based nucleosome footprinting and accessibility assays. Nuclei are treated with methyltransferase M.CviPI followed by bisulfite-seq [21,22]. | Kelly et al. 2012 Nabilsi et al. 2014 |
| dSMF | Dual-enzyme single-molecule footprinting. Treated nuclei with methyltransferases M.SssI and M.CviPI followed by bisulfite-seq of 300 bp fragments [23]. | Krebs et al. 2017 |
| Fiber-seq | Chromatin footprinting in nuclei with N6-adenine methyltransferases (Btr192IV, EcoGI, EcoGII, Hia5, or Hin1523) followed by long-read sequencing (PacBio) [24]. | Stergachis et al. 2020 |
| SAMOSA | Similar to Fiber-seq. Used M.EcoGII. Has been applied to in vitro chromatin arrays and to low nuclei samples [25]. | Abdulhay et al. 2020 |
| SMAC-Seq | Similar to Fiber-seq and SAMOSA, except that cells were treated with M.CviPI, M.EcoGII, and M.SssI. Long-read libraries were sequenced with Nanopore [26]. | Shipony et al. 2020 |
| ATAC-see, ATAC-PALM | Attached fluorophores onto the Tn5 adapters that allow for visualization of hyper-accessible regions by standard or super-resolution fluorescence microscopy. Can also sequence the samples using modified ATAC-seq protocol [27,28]. | Chen et al. 2016 Xie et al. 2020 |
| dCas9 live tracking | Accessibility measured by microscopy-based protein tracking and binding kinetics of single-molecule dCas9 particles that have been targeted to a specific locus or loci [29,30]. | Knight et al. 2015 Fu et al. 2016 |
| Micro-C, Micro-C XL | Derivative of Hi-C that uses exonuclease digestion instead of restriction enzymes to capture both short-range contacts (>1kb) and mid- to long-range contacts (kb to Mb scale) [31,32]. | Hsieh et al. 2015 Hsieh et al. 2016 |
| RICC-seq | Uses ionizing radiation with sequencing to probe short-range chromatin contacts (>1kb) [33,34]. | Rydberg et al. 1998 Risca et al. 2017 |
| Loop-seq | High throughput in vitro assay to assess inherent DNA flexibility of genomic sequence [35]. | Basu et al. 2021 |
| Gradient-seq | Derivative of FAIRE-seq with an added sucrose gradient, which allows for assessing the physical properties of chromatin. Can also be coupled with mass spectrometry [36]. | Nicetto et al. 2019 |
| CATCH-IT | Determine long-term nucleosome dynamics using a chemical-based biotin-labeling, MNase digestion, and a biotin-streptavidin purification [37]. | Deal et al. 2010 |
| Time-ChIP | Derivative of SNAP-tag using a biotin pulse-chase strategy for determining long-term histone turnover [38]. | Deaton et al. 2016 |
| dCas9-DD-BirA | Similar to CATCH-IT and Time-ChIP, but uses in vivo BirA enzyme fused to dCas9 to label nucleosomes with biotin and determine long-term turnover rates by ChIP-seq [39]. | Escobar et al. 2019 |