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Mechanisms of OCT4-SOX2 motif readout on nucleosomes.
Science ( IF 41.845 ) Pub Date : 2020-06-26 , DOI: 10.1126/science.abb0074
Alicia K Michael,Ralph S Grand,Luke Isbel,Simone Cavadini,Zuzanna Kozicka,Georg Kempf,Richard D Bunker,Andreas D Schenk,Alexandra Graff-Meyer,Ganesh R Pathare,Joscha Weiss,Syota Matsumoto,Lukas Burger,Dirk Schübeler,Nicolas H Thomä

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.
更新日期:2020-06-26

 

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