Oct4 is a master regulator of pluripotency. Potential Oct4 interactors have been cataloged extensively but the manner and significance of these interactions are incompletely defined. Like other POU domain proteins, Oct4 is capable of binding to DNA in multiple configurations, however the relationship between these configurations and cofactor recruitment (and hence transcription output) are unknown. Here, we show that Oct4 interacts with common and unique proteins when bound to DNA in different configurations. One of these proteins is Jade1, a component of the HBO histone acetyltransferase complex. Jade1 preferentially associates with Oct4 when bound to More palindromic Octamer-Related Element (MORE) DNA sequences that bind Oct4 dimers and are associated with strong gene expression. We show that the Oct4 N-terminus is critical for this interaction. ChIP-seq using HBO1, the enzymatic component of the complex, identifies a preference for binding adjacent to Oct4 at MORE sites. Using purified recombinant proteins and nucleosome complexes, we show that the HBO1 complex acetylates histone H3K9 within nucleosomes more efficiently when Oct4 is co-bound to a MORE site. Histone acetylation is further increased when Oct4 is mutated to favor dimeric MORE binding. Cryo-electron microscopy reveals that Oct4 bound to a MORE near the nucleosome entry/exit site partially unwinds DNA from nucleosome core particles, and identifies additional mass associated with the HBO1 complex. These results identify a novel mechanism of transcriptional regulation by Oct4.
[doi:10.25345/C5057D46J]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Oct4 ; Cofactor ; ESCs ; Jade1 ; MORE motif ; Octamer motif ; DatasetType:Proteomics
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Dean Tantin, University of Utah, United States of America |
Submitting User: | YifanWu |
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