SNAP output for PDB entry 6t93 [SNAP web server]

PDB-id

6t93; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription

Method

cryo-EM (3.49 Å)

Summary

Nucleosome with oct4-sox2 motif at shl-6

Reference

Michael AK, Grand RS, Isbel L, Cavadini S, Kozicka Z, Kempf G, Bunker RD, Schenk AD, Graff-Meyer A, Pathare GR, Weiss J, Matsumoto S, Burger L, Schubeler D, Thoma NH (2020): "Mechanisms of OCT4-SOX2 motif readout on nucleosomes." Science, 368, 1460-1465. doi: 10.1126/science.abb0074.

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 OCT4 and SOX2. We determined TF engagement throughout a nucleosome at base-pair resolution in vitro, enabling cryo-EM structure determination at two preferred positions. Depending on motif location, OCT4-SOX2 differentially distort nucleosomal DNA. At one position, OCT4-SOX2 removes DNA from Histone H2A/Histone H3 (H2A/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-SOX2 and reveal how TFs distort nucleosomes to access chromatinized motifs.