|Title||Mechanisms of OCT4-SOX2 motif readout on nucleosomes.|
|Journal, issue, pages||Science, Vol. 368, Issue 6498, Page 1460-1465, Year 2020|
|Publish date||Jun 26, 2020|
|Authors||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 /|
|PubMed Abstract||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 ...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.|
|External links||Science / PubMed:32327602|
|Methods||EM (single particle)|
|Resolution||3.05 - 3.49 Å|
|Keywords||Animals / Cryoelectron Microscopy / DNA / Gene Expression Regulation / Histones / Mice / Mouse Embryonic Stem Cells / Nucleosomes / Octamer Transcription Factor-3 / Pou5f1 protein, mouse / SOXB1 Transcription Factors / Sox2 protein, mouse / TRANSCRIPTION / nucleosome / OCT4 / SOX2 / transcription factor|
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