6T90

OCT4-SOX2-bound nucleosome - SHL-6

Summary for 6T90

• Entry DOI: 10.2210/pdb6t90/pdb
• EMDB information: 10406
• Descriptor: Histone H3.1, PENTANEDIAL, Histone H4, ... (10 entities in total)
• Functional Keywords: nucleosome, oct4, sox2, transcription factor, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 288373.44

Authors

Michael, A.K.,Kempf, G.,Cavadini, S.,Bunker, R.D.,Thoma, N.H. (deposition date: 2019-10-25, release date: 2020-05-06, Last modification date: 2024-10-23)

Primary citation

Michael, A.K.,Grand, R.S.,Isbel, L.,Cavadini, S.,Kozicka, Z.,Kempf, G.,Bunker, R.D.,Schenk, A.D.,Graff-Meyer, A.,Pathare, G.R.,Weiss, J.,Matsumoto, S.,Burger, L.,Schubeler, D.,Thoma, N.H.
Mechanisms of OCT4-SOX2 motif readout on nucleosomes.
Science, 368:1460-1465, 2020

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 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.

PubMed: 32327602
DOI: 10.1126/science.abb0074

Experimental method

ELECTRON MICROSCOPY (3.05 Å)