Pioneer factors as master regulators of the epigenome and cell fate

Balsalobre, Aurélio; Drouin, Jacques

doi:10.1038/s41580-022-00464-z

Cited by 159 publications

(114 citation statements)

References 174 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

Section: Resultsmentioning

confidence: 87%

“…Additionally, the binding of TFs is influenced by other factors including the presence of histone modifications, chromatin accessibility and 3D chromatin organization. A smaller subset of TFs, known as pioneers, are even able to influence chromatin accessibility by opening previously closed chromatin regions, thereby initiating and enabling subsequent binding of other factors [4] . Thus, a higher level of enhancer organization is a prominent factor in gene regulation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

TF-COMB – Discovering grammar of transcription factor binding sites

Bentsen

Heger

Schultheis

et al. 2022

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

TF-COMB – Discovering grammar of transcription factor binding sites

Bentsen

Heger

Schultheis

et al. 2022

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

“…Furthermore, this might also hint to additional characteristics of grammar, such as changes between biological conditions. Exemplary, the FOXA2-GATA4 pair, which was recently described as liver specific [4], differs between HepG2 and GM12878 cell lines (Figure 5d). In contrast, the ubiquitous pair NFYB-NFYC, which is known to form the trimeric NFY complex in collaboration with NFYA [42], remains similar between different cell lines (Supplementary Figure S5d).…”

Section: Resultsmentioning

confidence: 94%

TF-COMB - discovering grammar of transcription factor binding sites

Bentsen

Heger

Schultheis

et al. 2022

Preprint

View full text Add to dashboard Cite

Cooperativity between transcription factors is important to regulate target gene expression. In particular, the binding grammar of TFs in relation to each other, as well as in the context of other genomic elements, is crucial for TF functionality. However, tools to easily uncover co-occurrence between DNA-binding proteins, and investigate the regulatory modules of TFs, are limited. Here we present TF-COMB (Transcription Factor Co-Occurrence using Market Basket analysis) - a tool to investigate co-occurring TFs and binding grammar within regulatory regions. We found that TF-COMB can accurately identify known co-occurring TFs from ChIP-seq data, as well as uncover preferential localization to other genomic elements. With the use of ATAC-seq footprinting and TF motif locations, we found that TFs exhibit both preferred orientation and distance in relation to each other, and that these are biologically significant. Finally, we extended the analysis to not only investigate individual TF pairs, but also TF pairs in the context of networks, which enabled the investigation of TF complexes and TF hubs. In conclusion, TF-COMB is a flexible tool to investigate various aspects of TF binding grammar.

show abstract

“…GRHL2 is a pioneering transcription factor that can bind to closed chromatin and initiate its opening (Chen et al, 2018;Balsalobre and Drouin, 2022). Although our mechanism-based mathematical model does not incorporate epigenetic interactions, the ability of GRHL2 to influence chromatinlevel reprogramming further elevates its potency as a strong MET inducer (Chung et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

The ELF3 transcription factor is associated with an epithelial phenotype and represses epithelial-mesenchymal transition

Subbalakshmi

Sahoo

Manjunatha

et al. 2022

Preprint

View full text Add to dashboard Cite

Epithelial-mesenchymal plasticity (EMP) involves bidirectional transitions between epithelial, mesenchymal and multiple intermediary hybrid epithelial/mesenchymal phenotypes. While the process of epithelial-mesenchymal transition (EMT) and its associated transcription factors are well-characterised, the transcription factors that promote mesenchymal-epithelial transition (MET) and stabilise hybrid E/M phenotypes are less well understood. Here, we analyse multiple publicly-available transcriptomic datasets at bulk and single-cell level and pinpoint ELF3 as a factor that is strongly associated with an epithelial phenotype and is inhibited during EMT. Using mechanism-based mathematical modelling, we also show that ELF3 inhibits the progression of EMT, suggesting ELF3 may be able to counteract EMT induction, including in the presence of EMT-inducing factors, such as WT1. Our model predicts that the MET induction capacity of ELF3 is stronger than that of KLF4, but weaker than that of GRHL2. Finally, we show that ELF3 levels correlates with worse patient survival in a subset of solid tumor types, suggesting cell-of-origin or lineage specificity in the prognostic capacity of ELF3.

show abstract

Pioneer factors as master regulators of the epigenome and cell fate

Cited by 159 publications

References 174 publications

TF-COMB – Discovering grammar of transcription factor binding sites

TF-COMB – Discovering grammar of transcription factor binding sites

TF-COMB - discovering grammar of transcription factor binding sites

The ELF3 transcription factor is associated with an epithelial phenotype and represses epithelial-mesenchymal transition

Contact Info

Product

Resources

About