Journal
PLOS GENETICS
Volume 16, Issue 1, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1008546
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Funding
- Max Planck Society
- Human Frontier Science Program Career Development Award [CDA00060/2012]
- Bergen Research Foundation
- Norwegian Research Council [250049]
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Author summary In eukaryotes, DNA is packed inside the cell nucleus in the form of chromatin, which consists of DNA, proteins such as histones, and RNA. Chromatin accessibility influences when and where DNA-binding proteins such as transcription factors and RNA polymerase II find their targets in order to activate transcription. It is unclear, however, whether the accessibility of regulatory regions precedes and predicts future transcription. To address these questions, we took advantage of ATAC-seq, which is a powerful technique to probe chromatin accessibility states. We analyzed zebrafish embryos as they gear up to start transcription for the first time and related the accessibility of regulatory regions to the activity of associated genes. This revealed that chromatin at regulatory regions is often accessible prior to gene activity and that this has predictive value for future transcription. Analyzing transcription factor mutants, we further determined that Pou5f3, Sox19b and Nanog play an important role in opening up chromatin. Thus, our study shows that transcription factors open regulatory elements to prime gene activity during development. In many organisms, early embryonic development is driven by maternally provided factors until the controlled onset of transcription during zygotic genome activation. The regulation of chromatin accessibility and its relationship to gene activity during this transition remain poorly understood. Here, we generated chromatin accessibility maps with ATAC-seq from genome activation until the onset of lineage specification. During this period, chromatin accessibility increases at regulatory elements. This increase is independent of RNA polymerase II-mediated transcription, with the exception of the hypertranscribed miR-430 locus. Instead, accessibility often precedes the transcription of associated genes. Loss of the maternal transcription factors Pou5f3, Sox19b, and Nanog, which are known to be required for zebrafish genome activation, results in decreased accessibility at regulatory elements. Importantly, the accessibility of regulatory regions, especially when established by Pou5f3, Sox19b and Nanog, is predictive for future transcription. Our results show that the maternally provided transcription factors Pou5f3, Sox19b, and Nanog open up chromatin and prime genes for activity during zygotic genome activation in zebrafish.
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