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• W4206454429 abstract "Abstract Nucleosomes in eukaryotic genomes present a barrier to the competent binding of many regulatory proteins. Pioneer transcription factors (pTFs) can bind their target sites on nucleosomal DNA and collaborate with other factors to locally open chromatin and promote transcription. While the interaction of pluripotency pioneer factors and functional partners Sox2 and Oct4 with nucleosomes has been widely studied, molecular details about their engagement in different nucleosome contexts remain elusive. Here, using high-resolution nuclear magnetic resonance (NMR) spectroscopy and biochemical studies, we reveal site-specific structural and dynamic information about pTF interaction with nucleosomes. We find that the affinity of Sox2 and Oct4 to the nucleosome and their synergistic binding correlates with solvent-exposed sites but is highly position and DNA sequence dependent and linked to distinct pTF conformation and dynamics. Sox2 alone forms a super-stable complex near superhelical location 5 (SHL5) with similar affinity and conformation to that of naked DNA but shows elevated dynamics at suboptimal positions. Oct4 strongly favors positions near SHL5.5 and SHL6.5 and both of its DNA binding modules, POU S or POU HD , are required for stable complex formation. A ternary complex forms efficiently on canonical Sox2-Oct4 composite motifs (no spacing) near nucleosome ends but is sparse at spaced motifs and absent at internal sites. Moreover, the ability of Sox2 to fold and bend DNA plays a key role in the formation of a stable nucleosome complex and cooperative Oct4 binding. Collectively, our findings describe diverse binding modes of Sox2 and Oct4 on nucleosomes that could guide their site selection and potential interaction with other chromatin factors in vivo ." @default.
• W4206454429 created "2022-01-26" @default.
• W4206454429 creator A5051137425 @default.
• W4206454429 creator A5065621265 @default.
• W4206454429 date "2022-01-21" @default.
• W4206454429 modified "2023-10-14" @default.
• W4206454429 title "Nucleosome topology and DNA sequence modulate the engagement of pioneer factors SOX2 and OCT4" @default.
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• W4206454429 doi "https://doi.org/10.1101/2022.01.18.476780" @default.
• W4206454429 hasPublicationYear "2022" @default.
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