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-Structure paper
Title | Structural mechanism of LIN28B nucleosome targeting by OCT4. |
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Journal, issue, pages | Mol Cell, Vol. 83, Issue 12, Page 1970-11982.e6, Year 2023 |
Publish date | Jun 15, 2023 |
Authors | Ruifang Guan / Tengfei Lian / Bing-Rui Zhou / David Wheeler / Yawen Bai / |
PubMed 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 ...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. |
External links | Mol Cell / PubMed:37327775 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.6 - 7.9 Å |
Structure data | EMDB-26258, PDB-7u0g: EMDB-26260, PDB-7u0i: EMDB-26261, PDB-7u0j: EMDB-27483, PDB-8dk5: EMDB-40683, PDB-8sps: EMDB-40684: Low resolution reconstruction of ESRRB nucleosome bound OCT4 at site a and site b EMDB-40686, PDB-8spu: EMDB-40691: Focused classification of site c OCT4 |
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Keywords | TRANSCRIPTION/DNA / nucleosome / transcription factor / transcription / CHROMATIN BINDING PROTEIN-DNA complex / TRANSCRIPTION-DNA complex / GENE REGULATION |