Abstract:
:While recent experiments revealed that some pioneer transcription factors (TFs) can bind to their target DNA sequences inside a nucleosome, the binding dynamics of their target recognitions are poorly understood. Here we used the latest coarse-grained models and molecular dynamics simulations to study the nucleosome-binding procedure of the two pioneer TFs, Sox2 and Oct4. In the simulations for a strongly positioning nucleosome, Sox2 selected its target DNA sequence only when the target was exposed. Otherwise, Sox2 entropically bound to the dyad region nonspecifically. In contrast, Oct4 plastically bound on the nucleosome mainly in two ways. First, the two POU domains of Oct4 separately bound to the two parallel gyres of the nucleosomal DNA, supporting the previous experimental results of the partial motif recognition. Second, the POUS domain of Oct4 favored binding on the acidic patch of histones. Then, simulating the TFs binding to a genomic nucleosome, the LIN28B nucleosome, we found that the recognition of a pseudo motif by Sox2 induced the local DNA bending and shifted the population of the rotational position of the nucleosomal DNA. The redistributed DNA phase, in turn, changed the accessibility of a distant TF binding site, which consequently affected the binding probability of a second Sox2 or Oct4. These results revealed a nucleosomal DNA-mediated allosteric mechanism, through which one TF binding event can change the global conformation, and effectively regulate the binding of another TF at distant sites. Our simulations provide insights into the binding mechanism of single and multiple TFs on the nucleosome.
journal_name
Proc Natl Acad Sci U S Aauthors
Tan C,Takada Sdoi
10.1073/pnas.2005500117subject
Has Abstractpub_date
2020-08-25 00:00:00pages
20586-20596issue
34eissn
0027-8424issn
1091-6490pii
2005500117journal_volume
117pub_type
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