Cell
Volume 161, Issue 3, 23 April 2015, Pages 555-568
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Article
Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming

https://doi.org/10.1016/j.cell.2015.03.017Get rights and content
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Highlights

  • Oct4, Sox2, Klf4, and Myc show a range of affinities to nucleosomes

  • Oct4, Sox2, and Klf4 target partial motifs exposed on nucleosomes

  • c-Myc recognizes degenerate E-box motifs on nucleosomes with other factors

  • DBD recognition of motifs on nucleosome surface determines pioneer activity

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 naive chromatin sites.

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Present address: MRC Centre for Regenerative Medicine, SCRM Building, University of Edinburgh, Edinburgh Bioquarter, 5 Little France Drive, Edinburgh EH16 4UU, UK