ArticleGenome research2021
A flexible repertoire of transcription factor binding sites and a diversity threshold determines enhancer activity in embryonic stem cells.
Article in Genome research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- A transcription factor by any other name - function beyond DNA binding and transactivation.EMBO reports · 2026Review
- iEnhancer-Flow: Integrating Transformer-Based Sequence Learning with DNA Shape Insights for Robust Enhancer Prediction.Interdisciplinary sciences, computational life sciences · 2026Article
- High-resolution map of chromatin accessibility - insights into the focused binding of a large number of transcription factors.Epigenetics & chromatin · 2026Article
- Motif-based models accurately predict cell type-specific distal regulatory elements.Nature communications · 2025Article
- Master transcription-factor binding sites constitute the core of early replication control elements.The EMBO journal · 2025Article
- JUND plays a genome-wide role in the quiescent to contractile switch in the pregnant human myometrium.PLoS genetics · 2025Article
- Interpreting regulatory mechanisms of Hippo signaling through a deep learning sequence model.Cell genomics · 2025Article
- AnFrontiers in genetics · 2025Article
- The cells are all-right: Regulation of the Lefty genes by separate enhancers in mouse embryonic stem cells.PLoS genetics · 2024Article
- cBAF generates subnucleosomes that expand OCT4 binding and function beyond DNA motifs at enhancers.Nature structural & molecular biology · 2024Article
- Identifying transcription factors with cell-type specific DNA binding signatures.BMC genomics · 2024Article
- Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids.Scientific reports · 2024Article
- Transcription factor interactions explain the context-dependent activity of CRX binding sites.PLoS computational biology · 2024Article
- A suboptimal OCT4-SOX2 binding site facilitates the naïve-state specific function of a Klf4 enhancer.PloS one · 2024Article
- SOX4 exerts contrasting regulatory effects on labor-associated gene promoters in myometrial cells.PloS one · 2024Article
- Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma.Nucleic acids research · 2023Article
- Clustered and diverse transcription factor binding underlies cell type specificity of enhancers for housekeeping genes.Genome research · 2023Article
- Characterization of enhancer activity in early human neurodevelopment using Massively parallel reporter assay (MPRA) and forebrain organoids.bioRxiv : the preprint server for biology · 2023Article
- Decoding enhancer complexity with machine learning and high-throughput discovery.Genome biology · 2023Review
- Novel enhancers conferring compensatory transcriptional regulation of Nkx2-5 in heart development.iScience · 2023Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Transcriptional enhancers are critical for development and phenotype evolution and are often mutated in disease contexts; however, even in well-studied cell types, the sequence code conferring enhancer activity remains unknown. To examine the enhancer regulatory code for pluripotent stem cells, we identified genomic regions with conserved binding of multiple transcription factors in mouse and human embryonic stem cells (ESCs). Examination of these regions revealed that they contain on average 12.6 conserved transcription factor binding site (TFBS) sequences. Enriched TFBSs are a diverse repertoire of 70 different sequences representing the binding sequences of both known and novel ESC regulators. Using a diverse set of TFBSs from this repertoire was sufficient to construct short synthetic enhancers with activity comparable to native enhancers. Site-directed mutagenesis of conserved TFBSs in endogenous enhancers or TFBS deletion from synthetic sequences revealed a requirement for 10 or more different TFBSs. Furthermore, specific TFBSs, including the POU5F1:SOX2 comotif, are dispensable, despite cobinding the POU5F1 (also known as OCT4), SOX2, and NANOG master regulators of pluripotency. These findings reveal that a TFBS sequence diversity threshold overrides the need for optimized regulatory grammar and individual TFBSs that recruit specific master regulators.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.