SNAP output for PDB entry 8dk5 [SNAP web server]

PDB-id

8dk5; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription-DNA

Method

cryo-EM (2.71 Å)

Summary

Structure of 187bp lin28b nucleosome with site 0 mutation

Reference

Guan R, Lian T, Zhou BR, Wheeler D, Bai Y (2023): "Structural mechanism of LIN28B nucleosome targeting by OCT4." Mol.Cell, 83, 1970-1982.e6. doi: 10.1016/j.molcel.2023.05.030.

Abstract

Pioneer transcription factors are essential for cell fate changes by targeting closed chromatin. OCT4 is a crucial pioneer factor that can induce cell reprogramming. However, the structural basis of how pioneer factors recognize the in vivo nucleosomal DNA targets is unknown. Here, we determine the high-resolution structures of the nucleosome containing human LIN28B DNA and its complexes with the OCT4 DNA binding region. Three OCT4s bind the pre-positioned nucleosome by recognizing non-canonical DNA sequences. Two use their POUS domains while the other uses the POUS-loop-POUHD region; POUHD serves as a wedge to unwrap ∼25 base pair DNA. Our analysis of previous genomic data and determination of the ESRRB-nucleosome-OCT4 structure confirmed the generality of these structural features. Moreover, biochemical studies suggest that multiple OCT4s cooperatively open the H1-condensed nucleosome array containing the LIN28B nucleosome. Thus, our study suggests a mechanism of how OCT4 can target the nucleosome and open closed chromatin.