Mechanisms of OCT4-SOX2 motif readout on nucleosomes
Creators
- 1. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
- 2. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland ; Faculty of Science, University of Basel
- 3. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland ; Swiss Institute of Bioinformatics
Description
Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming factors OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution in vitro, enabling structure determination by cryo–electron microscopy at two preferred positions. Depending on motif location, OCT4 and SOX2 differentially distort nucleosomal DNA. At one position, OCT4-SOX2 removes DNA from histone H2A and histone H3; however, at an inverted motif, the TFs only induce local DNA distortions. OCT4 uses one of its two DNA-binding domains to engage DNA in both structures, reading out a partial motif. These findings explain site-specific nucleosome engagement by the pluripotency factors OCT4 and SOX2, and they reveal how TFs distort nucleosomes to access chromatinized motifs.
Files
Science Abstract.pdf
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