Transcriptional Poising Prior to the Midblastula Transition Underlies Dorsal Cell Fate Specification by the Wnt/Beta-Catenin Pathway

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Doctor of Philosophy (PhD)
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Cell & Molecular Biology
Wnt Signaling
Histone Methylation
Transcriptional Poising
Developmental Biology
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Blythe, Shelby A

Following fertilization in many multicellular organisms, zygotic transcription is suppressed for several hours and cell divisions, until a major embryonic transition termed the midblastula transition (MBT). Nevertheless, steps critical for later patterning of the embryo occur during this early stage. To address this question, we have optimized the chromatin immunoprecipitation technique to allow the investigation of pre-MBT chromatin architecture. We find that, in the context of transcriptional quiescence before the MBT in Xenopus, Wnt signaling through β-catenin primes dorsal gene expression by establishing transcriptionally poised chromatin architecture at target promoters. This is later resolved into active gene expression following the large-scale activation of zygotic transcription at the MBT. During pre-MBT dorsal specification, β-catenin interacts with a histone H3 methyltransferase activity that targets arginine 8 (R8). Recruitment of the arginine methyltransferase Prmt2 to β-catenin target promoters is necessary and sufficient to establish the dorsal developmental program, indicating that Prmt2-mediated histone H3R8 methylation plays a critical role downstream of β-catenin in establishing poised chromatin architecture and marking key organizer genes for later expression. This work demonstrates a mechanism whereby a signal transduction pathway can establish poised chromatin architecture at target genes, which could have implications for the regulation of gene regulatory networks during development. Additionally, our results suggest the possibility that transcriptional poising plays a broader role in maintaining zygotic genome silencing before the MBT.

Peter S. Klein
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