title: Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming.
abstract: 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.
authors.affiliation: Institute for Regenerative Medicine and Epigenetics Program, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Smilow Center for Translational Research, Building 421, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5157, USA.
authors.forename: Abdenour
authors.initials: A
authors.lastname: Soufi
authors.affiliation: Institute for Regenerative Medicine and Epigenetics Program, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Smilow Center for Translational Research, Building 421, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5157, USA.
authors.forename: Meilin Fernandez
authors.initials: MF
authors.lastname: Garcia
authors.affiliation: Department of Molecular, Cell and Developmental Biology, UCLA, Box 951606, Los Angeles, CA 90095-1606, USA.
authors.forename: Artur
authors.initials: A
authors.lastname: Jaroszewicz
authors.affiliation: Institute for Regenerative Medicine and Epigenetics Program, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Smilow Center for Translational Research, Building 421, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5157, USA.
authors.forename: Nebiyu
authors.initials: N
authors.lastname: Osman
authors.affiliation: Department of Molecular, Cell and Developmental Biology, UCLA, Box 951606, Los Angeles, CA 90095-1606, USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Institute for Regenerative Medicine and Epigenetics Program, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Smilow Center for Translational Research, Building 421, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5157, USA. Electronic address: zaret@upenn.edu.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Zaret
mesh_terms: D000595:Amino Acid Sequence; D054337:Cell Dedifferentiation; D065150:Cellular Reprogramming; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D008958:Models, Molecular; D009707:Nucleosomes / Q000378:metabolism*; D059372:Nucleotide Motifs; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000145:classification / Q000378:metabolism*
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D009707:Nucleosomes; D050814:Octamer Transcription Factor-3; D014157:Transcription Factors; D004247:DNA