Rapid and efficient degradation of endogenous proteins in vivo identifies stage-specific roles of RNA Pol II pausing in mammalian development Journal Article

   

Authors:	Abuhashem, A.; Lee, A. S.; Joyner, A. L.; Hadjantonakis, A. K.
Article Title:	Rapid and efficient degradation of endogenous proteins in vivo identifies stage-specific roles of RNA Pol II pausing in mammalian development
Abstract:	Targeted protein degradation methods offer a unique avenue to assess a protein's function in a variety of model systems. Recently, these approaches have been applied to mammalian cell culture models, enabling unprecedented temporal control of protein function. However, the efficacy of these systems at the tissue and organismal levels in vivo is not well established. Here, we tested the functionality of the degradation tag (dTAG) degron system in mammalian development. We generated a homozygous knock-in mouse with a FKBP12F36V tag fused to negative elongation factor b (Nelfb) locus, a ubiquitously expressed regulator of transcription. In our validation of targeted endogenous protein degradation across mammalian development and adulthood, we demonstrate that irrespective of the route of administration the dTAG system is non-toxic, rapid, and efficient in embryos from the zygote-to-mid-gestation stages. Additionally, acute depletion of NELFB revealed a specific role in zygote-to-2-cell development and zygotic genome activation (ZGA). © 2022 Elsevier Inc.
Keywords:	transcription; mouse embryo; zygote; pausing; nelf; degron; dtag; post-implantation; pre-implantation; zga
Journal Title:	Developmental Cell
Volume:	57
Issue:	8
ISSN:	1534-5807
Publisher:	Cell Press
Date Published:	2022-04-25
Start Page:	1068
End Page:	1080.e6
Language:	English
DOI:	10.1016/j.devcel.2022.03.013
PUBMED:	35421370
PROVIDER:	scopus
PMCID:	PMC9047393
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85128456728&doi=10.1016%2fj.devcel.2022.03.013&partnerID=40&md5=ed8131369672e9195560f1f9a7aa573f
Notes:	Article -- Export Date: 2 May 2022 -- Source: Scopus

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