Structural highlights
Function
A0A376KDN7_ECOLX Part of the ABC transporter complex MalEFGK involved in maltose/maltodextrin import. Binds maltose and higher maltodextrins.[RuleBase:RU365005]PO5F1_HUMAN Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3'). Forms a trimeric complex with SOX2 or SOX15 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206. Critical for early embryogenesis and for embryonic stem cell pluripotency.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007 Nov 30;131(5):861-72. PMID:18035408 doi:10.1016/j.cell.2007.11.019
- ↑ Guan R, Lian T, Zhou BR, Wheeler D, Bai Y. Structural mechanism of LIN28B nucleosome targeting by OCT4. Mol Cell. 2023 Jun 15;83(12):1970-1982.e6. PMID:37327775 doi:10.1016/j.molcel.2023.05.030
