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Nat Commun 2022 Oct 06;131:5887. doi: 10.1038/s41467-022-33429-z.
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Differential nuclear import sets the timing of protein access to the embryonic genome.

Nguyen T , Costa EJ , Deibert T , Reyes J , Keber FC , Tomschik M , Stadlmeier M , Gupta M , Kumar CK , Cruz ER , Amodeo A , Gatlin JC , Wühr M .

The development of a fertilized egg to an embryo requires the proper temporal control of gene expression. During cell differentiation, timing is often controlled via cascades of transcription factors (TFs). However, in early development, transcription is often inactive, and many TF levels stay constant, suggesting that alternative mechanisms govern the observed rapid and ordered onset of gene expression. Here, we find that in early embryonic development access of maternally deposited nuclear proteins to the genome is temporally ordered via importin affinities, thereby timing the expression of downstream targets. We quantify changes in the nuclear proteome during early development and find that nuclear proteins, such as TFs and RNA polymerases, enter the nucleus sequentially. Moreover, we find that the timing of nuclear proteins' access to the genome corresponds to the timing of downstream gene activation. We show that the affinity of proteins to importin is a major determinant in the timing of protein entry into embryonic nuclei. Thus, we propose a mechanism by which embryos encode the timing of gene expression in early development via biochemical affinities. This process could be critical for embryos to organize themselves before deploying the regulatory cascades that control cell identities.

PubMed ID: 36202846
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aurkb birc5 birc5l cdca8 creb1 cse1l ctnnb1 dbf4b gtf2b gtf2e2 gtf2h1 gtf3a h2bc21 incenp ipo11 ipo4 ipo5 ipo7 ipo9 kit kpna2 kpna3 kpna4 kpna6 kpna7 kpnb1 myc orc1 orc2 orc3 orc4 orc5 orc6 phf5a polr2a recql4 smad2 smarca4 ticrr tnpo1 tnpo2 tnpo3 trna xpo1 xpo4 xpo5 xpo6 xpo7 xpot ybx2 yy1 znf250
GO keywords: nucleocytoplasmic transport [+]

Article Images: [+] show captions
References [+] :
Abdallah, Ketamine Treatment and Global Brain Connectivity in Major Depression. 2017, Pubmed