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Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming

2015; Cell Press; Volume: 161; Issue: 3 Linguagem: Inglês

10.1016/j.cell.2015.03.017

1097-4172

Abdenour Soufi, Meilín Fernández García, Artur Jaroszewicz, Nebiyu Osman, Matteo Pellegrini, Kenneth S. Zaret,

RNA Interference and Gene Delivery

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.