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Nucleosomal DNA Dynamics Mediate Oct4 Pioneer Factor Binding by Jan Huertas; Caitlin M. MacCarthy; Hans R. Schöler; Vlad Cojocaru is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Nucleosomal DNA Dynamics Mediate Oct4 Pioneer Factor Binding about?

Transcription factor (TF) proteins bind to DNA to regulate gene expression. Normally, accessibility to DNA is required for their function. However, in the nucleus, the DNA is often inaccessible, wrapped around histone proteins in nucleosomes forming the chromatin. Pioneer TFs are thought to induce chromatin opening by recognizing their DNA binding sites on nucleosomes. For example, Oct4, a master regulator and inducer of stem cell pluripotency, binds to DNA in nucleosomes in a sequence-specific manner. Here, we reveal the structural dynamics of nucleosomes that mediate Oct4 binding from molecular dynamics simulations. Nucleosome flexibility and the amplitude of nucleosome motions such as breathing and twisting are enhanced in nucleosomes with multiple TF binding sites. Moreover, the regions around the binding sites display higher local structural flexibility. Probing different structures of Oct4-nucleosome complexes, we show that alternative configurations in which Oct4 recognizes partial binding sites display stable TF-DNA interactions similar to those observed in complexes with free DNA and compatible with the DNA curvature and DNA-histone interactions. Therefore, we propose a st

Who reads Nucleosomal DNA Dynamics Mediate Oct4 Pioneer Factor Binding?

Author

Jan Huertas; Caitlin M. MacCarthy; Hans R. Schöler; Vlad Cojocaru

Publisher

Elsevier BV

Published

2020

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)