Super-enhancer Profiling Service

Super-enhancers comprise of clusters of enhancers that are typically defined by the ChIP-seq analysis for active histone marks. CD BioSciences's super-enhancer profiling service provides a comprehensive analysis of super-enhancers in your biological samples, focusing on the scientific and technical details needed by biomedical researchers.

Introduction to Super-enhancer Profiling

Super-enhancers (SEs) are large clusters of enhancers that work together to drive unusually high expression of key genes, often those defining cell identity. In contrast to typical enhancers (which are individual regulatory DNA elements usually a few hundred base pairs long), super-enhancers span tens of kilobases-typically on the order of 8-20 kb or more-as multiple enhancer segments stitched together. They also recruit an exceptionally high density of transcription factors and co-activator proteins (like Mediator and BRD4), accumulating much stronger activation signals (e.g. H3K27ac marks) than regular enhancers. Due to this, super-enhancers can strongly activate their target genes, resulting in much higher gene expression levels compared to typical enhancer-driven genes.

Super-enhancer profiling is the genome-wide identification and characterization of these extended enhancer domains based on chromatin occupancy signals. This is typically achieved using ChIP-seq for enhancer-associated marks, including:

1. H3K27ac: Active enhancer acetylation mark (most widely used)
2. H3K4me1: Primed or poised enhancer mark
3. BRD4, MED1, or p300: Coactivators enriched at active regulatory regions
4. Pol II: Associated with active transcription initiation at SE targets

By mapping these chromatin features and quantifying their signal across enhancer clusters, researchers can distinguish high-density enhancer regions (super-enhancers) from typical enhancer elements. Super-enhancers are often defined as those stitched enhancer regions whose cumulative signal lies above an inflection point when plotted in rank order.

Fig.1 Super-enhancer profiling in AML samples. Enhancers were ranked by increasing H3K27ac signal in 11 AML samples. (Fang, F., et al., 2022)

Applications of Super-enhancer Profiling

1. Identification of cell identity or disease-defining genes
2. Mapping core regulatory elements in differentiation, cancer, immunology
3. Integration with drug response, CRISPR screens, or multi-omics
4. Target prioritization for epigenetic or transcriptional therapies
5. Discovery of transcriptional dependencies and vulnerability nodes

Our Services

Our super-enhancer profiling service follows a rigorous step-by-step workflow–from sample preparation through data analysis – to produce reliable and insightful results.

Sample Processing & ChIP-seq

1. Accepts cells or tissues (fresh/frozen)
2. ChIP-grade chromatin preparation
3. ChIP-seq targeting H3K27ac, H3K4me1, MED1, BRD4, or Pol II

Enhancer Calling & Stitching

1. Peak calling for enhancer-associated marks
2. Stitched enhancer domains created by joining peaks within ≤12.5 kb
3. Promoter-proximal regions excluded to reduce

Super-enhancer Ranking

1. Enhancer domains ranked by signal strength
2. Inflection point used to define super-enhancer threshold
3. Typical and super-enhancer sets distinguished

Annotation & Interpretation

1. Gene assignment based on proximity or known loops
2. GO and pathway enrichment of SE-regulated genes
3. Visualization via IGV/UCSC, SE ranking plots, genomic tracks

Supported Sample Types

1. Cultured Cells (e.g., cancer)
2. Fresh-Frozen Tissues
3. Xenograft-Derived Tissue or Organoids

1. Primary Cells or Sorted Subpopulations
2. Patient-Derived Samples
3. Other Types (Please Inquire)

Our Advantages

1. Multiple Anchor Options: Compatible with H3K27ac, BRD4, MED1, Pol II, or p300 for enhancer identification.
2. Quantitative Enhancer Ranking: Enhancer clusters ranked via signal intensity and stitched domains.
3. Gene Regulatory Mapping: SE–gene linkage with GO and pathway enrichment output.
4. Disease & Oncogene Discovery: Ideal for identifying transcriptional dependencies and target prioritization.
5. Visualization & Integration Ready: Delivers genome tracks, SE plots, and integrates with RNA-seq/CRISPR.
6. Validated Across Models: Applicable to hematologic malignancies, solid tumors, and normal lineage systems.

Super-enhancers represent a small fraction of the enhancer landscape but exert disproportionate control over transcriptional output. By profiling these regions, researchers gain insight into the regulatory infrastructure that governs cell state and disease. Whether you're mapping developmental transitions, dissecting cancer circuits, or exploring drug-sensitive regulators, CD BioSciences's Super-enhancer Profiling Service provides a powerful framework to illuminate the highest-priority enhancer-gene axes in your system. Contact us to begin your super-enhancer discovery project.

Reference

1. Fang, F., et al. (2022). Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia. Journal of experimental & clinical cancer research : CR, 41(1), 225.