Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming
By A. Soufi, M. F. Garcia, Artur Jaroszewicz, Nebiyu Osman, Matteo Pellegrini, K. Zaret. Cell, 2015
725 citations recorded by the source corpus.
SUMMARY Pioneer transcription factors (TFs) access silent chromatin and initiate cell fate changes, using diverse types of DNA binding domains (DBDs). FoxA, the paradigm pioneer TF, has a winged helix DBD that resembles linker histone and thereby binds its target sites on nucleosomes and in compacted chromatin. Herein we compare the nucleosome and chromatin targeting activities of Oct4 (POU DBD), Sox2 (HMG box DBD), Klf4 (zinc finger DBD), and c-Myc (bHLH DBD), which together reprogram somatic cells to pluripotency. Purified Oct4, Sox2, and Klf4 proteins can bind nucleosomes in vitro, and in vivo they preferentially target silent sites enriched for nucleosomes. Pioneer activity relates simply to the ability of a given DBD to target partial motifs displayed on the nucleosome surface. Such partial motif recognition can occur by coordinate binding between factors. Our findings provide insight into how pioneer factors can target naïve chromatin sites.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/0a23a104294ce4318a90a1c70248de6cc65b2f1f
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Citations in the corpus
- The Human Transcription Factors. (2018, neutral): “For instance, weakening of a TCF7L2 (TCF-4)-binding site within an enhancer that drives expression of MYC can decrease risk for tumorigenesis in the colon (reviewed in Sur and Taipale [2016]).”
- MYC, Metabolism, and Cancer. (2015, background): “Indeed, recent work suggests a centrally degenerate E-box motif in closed chromatin may be accessible to MYC using a partially unfolded DNA-binding domain when assisted by other factors, adding a structural rationale to the idea that MYC’s ability to affect gene expression is a confluence of DNA con”
- Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo (2015, background): “Furthermore, Pou5f3 and Sox2 are known to be pioneer factors instrumental in reprogramming differentiated cells to a pluripotent state (Soufi et al. 2012, 2015).”