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Structural mechanism of synergistic targeting of the nucleosome by PU1 and C/EBPα

biorxiv. 2023-08; 
Tengfei Lian, Ruifang Guan, Bing-Rui Zhou, Yawen Bai
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Gene Synthesis … ETS ( ETS PU.1, residues 165–272) with an N-terminal His-tag and DBD of C/EBPα (residues 214–359) with a C-terminal His-tag were directly synthesized in GenScript. Q218H and … Get A Quote

摘要

Pioneer transcription factors are vital for cell fate changes. PU.1 and C/EBPα work together to regulate hematopoietic stem cell differentiation. However, how they recognize nucleosomal DNA targets remain elusive. Here we report the structures of the nucleosome containing the mouse genomic enhancer DNA and its complexes with PU.1 alone and with both PU.1 and the C/EBPα DNA binding domain. Our structures reveal that PU.1 binds the DNA motif at the exit linker, shifting 17 bp of DNA into the core region through interactions with H2A, unwrapping ~20 bp of nucleosomal DNA. C/EBPα binding, aided by PU.1's repositioning, unwraps ~25 bp entry DNA. The PU.1 Q218H mutation, linked to acute myeloid leukemia, disrupt... More

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