# Research timeline and gaps: Super-enhancer Model of Cell Identity

Selected publication milestones, not an exhaustive history or discovery priority claim.

**2013 — Operational Mediator-rich clusters are linked with cell-identity genes.** [Original PMID23582322](https://pubmed.ncbi.nlm.nih.gov/23582322/).

**2015 — Native constituent deletion identifies local regulatory interdependence.** [Original PMID25801169](https://pubmed.ncbi.nlm.nih.gov/25801169/).

**2016 — Alpha-globin allelic series tests apparent additive contributions.** [Original PMID27376235](https://pubmed.ncbi.nlm.nih.gov/27376235/).

**2016 — Mammary motif combinations distinguish hierarchy and tested pairwise addition.** [Original PMID27376239](https://pubmed.ncbi.nlm.nih.gov/27376239/).

**2017 — Native conventional and called-cluster comparisons expose functional heterogeneity.** [Original PMID27895109](https://pubmed.ncbi.nlm.nih.gov/27895109/).

**2019 — Native retinal enhancer-region deletion changes cell composition and vision.** [Original PMID31493975](https://pubmed.ncbi.nlm.nih.gov/31493975/).

**2023 — Native reconstruction reveals activators and position-dependent facilitators.** [Original PMID38101409](https://pubmed.ncbi.nlm.nih.gov/38101409/).

**2025 — Cluster inversion adds an endogenous orientation and targeting test.** [Original PMID39863595](https://pubmed.ncbi.nlm.nih.gov/39863595/).

## Research gaps

Test SEs against activity-, length-, constituent-number- and promoter-matched conventional clusters, rather than weak isolated enhancers.

Use reconstruction and higher-order combinations to avoid missing interactions masked by single deletions.

Separate transcriptional output, physiological specialization, lineage formation and maintenance of cell identity.

Define a nonadditive null model on an explicit output scale, with uncertainty, saturation and promoter limits.

Resolve facilitator position, sequence, promoter compatibility and developmental redundancy across independent loci.

Separate coactivator protein dependence from condensate-phase-specific function and drug pleiotropy.

Audit linked correction bodies for the alpha-globin inversion, Myc cluster, Gasperini screen and Du study before publication; resolve the muscle abstract descriptor inconsistency.

## Boundary experiment

Compare a prespecified multi-lineage panel of high-ChIP clusters and conventional clusters matched for constituent number, occupancy, baseline output, spacing and promoter compatibility using native combinatorial deletions and reconstruction with lineage-state tracking.