TY - JOUR
T1 - Differential nuclear import sets the timing of protein access to the embryonic genome
AU - Nguyen, Thao
AU - Costa, Eli J.
AU - Deibert, Tim
AU - Reyes, Jose
AU - Keber, Felix C.
AU - Tomschik, Miroslav
AU - Stadlmeier, Michael
AU - Gupta, Meera
AU - Kumar, Chirag K.
AU - Cruz, Edward R.
AU - Amodeo, Amanda
AU - Gatlin, Jesse C.
AU - Wühr, Martin
N1 - Funding Information:
We thank Matt Sonnett, Eyan Yeung, Lillia Ryazanov, Nick Treen for help and training and Eric Wieschaus, Mike Levine, Elizabeth Van Itallie, and members of the Wühr Laboratory for their comments and edits on the manuscript. We thank David Hill for access to the Xenopus ORFeome and Dirk Görlich, Thomas Güttler, and Sabine Petry for the gifts of RanQ69L and importin plasmids. We thank James Pelletier for his help with designing the filter holders. Lastly, we thank John Oakey and Cassidy Enloe for their help with PDMS device design and manufacture. This work was supported by NIH grant R35GM128813 (M.W.), P20-GM113132 (A.A.), R01GM135568 (J.G.), American Heart Association predoctoral fellowship 20PRE35220061 (T.N.), National Science Foundation Graduate Research Fellowship (E.R.C.), EMBO ALTF 601-2018 (F.C.K.), Princeton Catalysis Initiative (M.W.), Eric and Wendy Schmidt Transformative Technology Fund (M.W.), Harold W. Dodds Fellowship (M.G.), Princeton University’s Summer Undergraduate Research Program (E.C., J.R., C.K.), NSF MODULUS award 2052640 (J.G.).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-33429-z
DO - 10.1038/s41467-022-33429-z
M3 - Article
C2 - 36202846
AN - SCOPUS:85139372689
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5887
ER -