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. 2020 Sep 2;10(24):11049–11062. doi: 10.7150/thno.49168

Table 1.

Methods of super enhancer identification

Methods Description Advantages Disadvantages Ref.
ChIP-seq (Chromatin Immunoprecipitation sequencing) A method for detecting genome-wide DNA segments interacting with histones and transcription factors. 1) Provides a high-resolution map of genomic expression regulation with less samples;
2) No signal noise deviations as direct sequencing method is used.
1) Unstable data accuracy as it is greatly influenced by the quality of antibodies;
2) High cost of building ChIP-seq workflow.
14, 15
3C-seq (Chromosome conformation capture) A method for detecting the DNA-DNA interactions between enhancer regions and one other transcriptional regulatory elements. 1) Combine with quantitative PCR (qPCR) to reveal the results quantitatively;
2) No sequencing is required so the cost is low.
1) Low-throughput because interactions must be tested one at a time;
2) Not unbiased because genomic positions must be chosen to test for interactions.
16, 17
4C-seq (Circularized chromosome conformation capture) A method for detecting genome-wide DNA-DNA interactions with a single chosen genomic location of interest. 1) Provides a high-resolution map of chromatin interactions with a chosen 'viewpoint';
2) Fewer samples are needed for sufficient sequencing depth.
1) Inefficient because primers must be redesigned specifically before each 'viewpoint' tested;
2) Improvement is needed for data normalization and unbiased estimate.
17, 18
Hi-C (High-throughput chromosome conformation capture) A method for detecting pairwise contacts between virtually any pair of genomic loci. 1) A matrix-balancing normalization method associated with high-resolution sequencing is developed;
2) Combines with visualization platforms to construct the 3D structure of chromatin interaction.
1) High signal noise because of polymerization state and dynamic chromatin interactions;
2) Insufficient genome-wide resolution to bridge 3D information to gene function perfectly.
19, 20
STARR-seq (self-transcribing active regulatory region sequencing) A method to identify transcriptional enhancers and to assess their activity quantitatively by cloning DNA fragments downstream of a core promoter. 1) Provides genome-wide cell type-specific quantitative enhancer activity maps of any cell type;
2) Not affected by the location of the sequences.
Repeated identification may exist because of lack of accurate context markers. 21, 22