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Publication Abstract from PubMed

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 approximately 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.

Structural mechanism of LIN28B nucleosome targeting by OCT4.,Guan R, Lian T, Zhou BR, Wheeler D, Bai Y Mol Cell. 2023 Jun 15;83(12):1970-1982.e6. doi: 10.1016/j.molcel.2023.05.030. PMID:37327775^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.