Leading science, pioneering therapies
CRM Publications

Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming.

TitlePioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming.
Publication TypeJournal Article
Year of Publication2015
AuthorsSoufi A, Garcia MFernandez, Jaroszewicz A, Osman N, Pellegrini M, Zaret KS
JournalCell
Volume161
Issue3
Pagination555-68
Date Published2015 Apr 23
ISSN1097-4172
KeywordsAmino Acid Sequence, Cell Dedifferentiation, Cellular Reprogramming, DNA, Fibroblasts, Humans, Induced Pluripotent Stem Cells, Models, Molecular, Nucleosomes, Nucleotide Motifs, Octamer Transcription Factor-3, Protein Structure, Tertiary, Sequence Alignment, Transcription Factors
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.

DOI10.1016/j.cell.2015.03.017
Alternate JournalCell
PubMed ID25892221
PubMed Central IDPMC4409934
Grant ListP01 GM099134 / GM / NIGMS NIH HHS / United States
P01GM099134 / GM / NIGMS NIH HHS / United States
Publication institute
Other