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PXD028069

PXD028069 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDifferential nuclear import sets the timing of protein access to the embryonic genome
DescriptionDuring early embryonic cell divisions, the total nuclear volume doubles with each cycle. At a critical volume ratio between the nucleus and cytoplasm, embryos start transcribing their genome in a reproducible and sequential manner. However, the underlying molecular mechanism for these well-timed events remains unclear. Previous studies proposed that titration of a regulatory factor by the exponentially increasing DNA content of the system triggers the onset of the first transcripts. Nevertheless, a systematic investigation of nuclear proteome changes during development is still missing. In this study, we perform this investigation and find that differential nuclear import timing can largely explain the sequential onset of transcription. First, we investigated nuclear proteome changes in early development. We found that nuclear proteins sequentially titrate into the embryonic nuclei. Interestingly, transcription factors and RNA polymerases enter the nucleus at different times, which correspond to the activation of their nuclear functions. Notably, we observed a high correlation between when transcription factors enter the nucleus and the order in which they activate downstream transcription. Time-lapse imaging of protein import into nuclei encapsulated in droplets of cytoplasmic extract validated our discovery of the sequential nuclear import by mass spectrometry. Lastly, we investigated the underlying molecular mechanism responsible for the differential timing of protein entry into embryonic nuclei. To this end, we quantified the relative affinity of substrates to importin and observe that high-affinity substrates tend to enter the nucleus earlier than low-affinity substrates. Notably, we can explain > 36% of the observed time-variation of when proteins enter the nucleus in the embryo with this simple affinity assay. Together, our results suggest that embryos control protein entry into the nucleus by modulating importin affinities, which then determines the timing of essential nuclear processes in early development.
HostingRepositoryPRIDE
AnnounceDate2022-08-30
AnnouncementXMLSubmission_2022-08-29_20:47:46.151.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterThao Nguyen
SpeciesList scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-08-23 06:38:47ID requested
12022-08-29 20:47:46announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: zygotic gene activation, nucleocytoplasmic partitioning, early embryogenesis, Xenopus embryo, nuclear import, LC-MS, multiplexed quantitative proteomics
Contact List
Martin Helmut Wuhr
contact affiliationWuhr Lab, Molecular Biology and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, USA
contact emailwuhr@princeton.edu
lab head
Thao Nguyen
contact affiliationWuhr Lab - Princeton University
contact emailtn3@princeton.edu
dataset submitter
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Dataset FTP location
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