@article{3186a24a482c477890abeac53a50bae0,
title = "Developmentally Programmed Tankyrase Activity Upregulates β-Catenin and Licenses Progression of Embryonic Genome Activation",
abstract = "Embryonic genome activation (EGA) is orchestrated by an intrinsic developmental program initiated during oocyte maturation with translation of stored maternal mRNAs. Here, we show that tankyrase, a poly(ADP-ribosyl) polymerase that regulates β-catenin levels, undergoes programmed translation during oocyte maturation and serves an essential role in mouse EGA. Newly translated TNKS triggers proteasomal degradation of axin, reducing targeted destruction of β-catenin and promoting β-catenin-mediated transcription of target genes, including Myc. MYC mediates ribosomal RNA transcription in 2-cell embryos, supporting global protein synthesis. Suppression of tankyrase activity using knockdown or chemical inhibition causes loss of nuclear β-catenin and global reductions in transcription and histone H3 acetylation. Chromatin and transcriptional profiling indicate that development arrests prior to the mid-2-cell stage, mediated in part by reductions in β-catenin and MYC. These findings indicate that post-transcriptional regulation of tankyrase serves as a ligand-independent developmental mechanism for post-translational β-catenin activation and is required to complete EGA.",
keywords = "ATAC-seq, axin, embryonic genome activation, mouse, post-transcriptional regulation, preimplantation embryo, tankyrase, WNT signaling pathway, β-catenin",
author = "Andr{\'e}s Gambini and Paula Stein and Virginia Savy and Grow, {Edward J.} and Papas, {Brian N.} and Yingpei Zhang and Kenan, {Anna C.} and Elizabeth Padilla-Banks and Cairns, {Bradley R.} and Williams, {Carmen J.}",
note = "Funding Information: We thank Susan Smith (NYU) for tankyrase antibodies and Jurrien Dean, Richard Schultz, Paul Wade, and Guang Hu for manuscript critiques. This work was supported by the Intramural Research Program of the NIH , National Institutes of Environmental Health Sciences , 1ZIAES102985 (C.J.W.) and the Howard Hughes Medical Institute (B.R.C.). E.J.G. was supported by the Lalor Foundation Postdoctoral Fellowship and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the NIH (award number F32HD094500). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: We thank Susan Smith (NYU) for tankyrase antibodies and Jurrien Dean, Richard Schultz, Paul Wade, and Guang Hu for manuscript critiques. This work was supported by the Intramural Research Program of the NIH, National Institutes of Environmental Health Sciences, 1ZIAES102985 (C.J.W.) and the Howard Hughes Medical Institute (B.R.C.). E.J.G. was supported by the Lalor Foundation Postdoctoral Fellowship and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the NIH (award number F32HD094500). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conceptualization, A.G. P.S. and C.J.W.; Methodology, A.G. P.S. and E.J.G.; Formal Analysis, E.J.G. and B.N.P.; Investigation, A.G. E.J.G. P.S. V.S. Y.Z. A.C.K. and E.P.-B.; Writing ? Original Draft, A.G. and C.J.W.; Writing ? Review & Editing, A.G. E.J.G. P.S. V.S. B.N.P. A.C.K. E.P.-B. B.R.C. and C.J.W.; Visualization, A.G. E.J.G. P.S. B.N.P. E.P.-B. and C.J.W.; Supervision, B.R.C. and C.J.W; Funding Acquisition, B.R.C. and C.J.W. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = jun,
day = "8",
doi = "10.1016/j.devcel.2020.04.018",
language = "English (US)",
volume = "53",
pages = "545--560.e7",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "5",
}