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TitleMechanisms of OCT4-SOX2 motif readout on nucleosomes.
Journal, issue, pagesScience, Vol. 368, Issue 6498, Page 1460-1465, Year 2020
Publish dateJun 26, 2020
AuthorsAlicia 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 AbstractTranscription 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 linksScience / PubMed:32327602
MethodsEM (single particle)
Resolution3.05 - 3.49 Å
Structure data

EMDB-10406, PDB-6t90:
OCT4-SOX2-bound nucleosome - SHL-6
Method: EM (single particle) / Resolution: 3.05 Å

EMDB-10408, PDB-6t93:
Nucleosome with OCT4-SOX2 motif at SHL-6
Method: EM (single particle) / Resolution: 3.49 Å

EMDB-10864, PDB-6yov:
OCT4-SOX2-bound nucleosome - SHL+6
Method: EM (single particle) / Resolution: 3.42 Å

Chemicals

ChemComp-PTD:
PENTANEDIAL / medication*YM / Glutaraldehyde

Source
  • homo sapiens (human)
  • synthetic construct (others)
  • aequorea victoria (jellyfish)
KeywordsAnimals / 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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