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Role of TIF1α as a modulator of embryonic transcription in the mouse zygote

Torres-Padilla, Maria Elena and Zernicka-Goetz, Magdalena (2006) Role of TIF1α as a modulator of embryonic transcription in the mouse zygote. Journal of Cell Biology, 174 (3). pp. 329-338. ISSN 0021-9525. PMCID PMC2064229. doi:10.1083/jcb.200603146. https://resolver.caltech.edu/CaltechAUTHORS:20190419-105736755

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[img] Image (JPEG) (Figure S1 Typical BrUTP accumulation in late zygote and 2-cell stage embryos) - Supplemental Material
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[img] Image (JPEG) (Figure S2 RNAi for TIF1α in zygotes does not induce the down-regulation of TIF1β) - Supplemental Material
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[img] Image (JPEG) (Figure S3 Specificity of the TIF1α antibody used in this work) - Supplemental Material
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[img] Image (JPEG) (Figure S4 SNF2H coimmunoprecipitates with TIF1α in vivo) - Supplemental Material
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Abstract

The first events of the development of any embryo are under maternal control until the zygotic genome becomes activated. In the mouse embryo, the major wave of transcription activation occurs at the 2-cell stage, but transcription starts already at the zygote (1-cell) stage. Very little is known about the molecules involved in this process. We show that the transcription intermediary factor 1 α (TIF1α) is involved in modulating gene expression during the first wave of transcription activation. At the onset of genome activation, TIF1α translocates from the cytoplasm into the pronuclei to sites of active transcription. These sites are enriched with the chromatin remodelers BRG-1 and SNF2H. When we ablate TIF1α through either RNA interference (RNAi) or microinjection of specific antibodies into zygotes, most of the embryos arrest their development at the 2–4-cell stage transition. The ablation of TIF1α leads to mislocalization of RNA polymerase II and the chromatin remodelers SNF2H and BRG-1. Using a chromatin immunoprecipitation cloning approach, we identify genes that are regulated by TIF1α in the zygote and find that transcription of these genes is misregulated upon TIF1α ablation. We further show that the expression of some of these genes is dependent on SNF2H and that RNAi for SNF2H compromises development, suggesting that TIF1α mediates activation of gene expression in the zygote via SNF2H. These studies indicate that TIF1α is a factor that modulates the expression of a set of genes during the first wave of genome activation in the mouse embryo.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1083/jcb.200603146DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064229/PubMed CentralArticle
http://www.jcb.org/cgi/content/full/jcb.200603146/DC1PublisherSupporting Information
ORCID:
AuthorORCID
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2006 Rockefeller University Press. After the Initial Publication Period, RUP will grant to the public the non-exclusive right to copy, distribute, or display the Article under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode, or updates thereof. Submitted: 27 March 2006. Accepted: 7 July 2006. We are grateful to Dr. R. Losson for kindly providing the pSK.TIF1a plasmid, Dr. P. Varga-Weisz for the hSNF2H antibody, Dr. B. Turner for the acetylK14 H3 antibody, and C. Lee for the mouse embryonic fibroblasts. We thank R. Schneider, S. Daujat, P. Varga-Weisz, and K. Ancelin for helpful discussions and A. Bannister, R. Livesely, and J. Pines for critical reading of the manuscript. The initial phase of this work was supported by a Human Frontier Science Program grant awarded to R. Pedersen, J. Rossant, and M. Zernicka-Goetz. This work was supported by the Wellcome Trust. M. Zernicka-Goetz is a Wellcome Trust Senior Research Fellow. M.-E. Torres-Padilla is the recipient of a European Molecular Biology Organization long-term fellowship (ALT 2-2003).
Funders:
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
Wellcome TrustUNSPECIFIED
European Molecular Biology Organization (EMBO)ALT 2-2003
Issue or Number:3
PubMed Central ID:PMC2064229
DOI:10.1083/jcb.200603146
Record Number:CaltechAUTHORS:20190419-105736755
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190419-105736755
Official Citation:Role of TIF1α as a modulator of embryonic transcription in the mouse zygote Maria Elena Torres-Padilla, Magdalena Zernicka-Goetz The Journal of Cell Biology Jul 2006, 174 (3) 329-338; DOI: 10.1083/jcb.200603146
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94810
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:23 Apr 2019 16:21
Last Modified:16 Nov 2021 17:08

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