Developmentally Programmed Tankyrase Activity Upregulates β-Catenin and Licenses Progression of Embryonic Genome Activation

Andrés Gambini, Paula Stein, Virginia Savy, Edward J. Grow, Brian N. Papas, Yingpei Zhang, Anna C. Kenan, Elizabeth Padilla-Banks, Bradley R. Cairns, Carmen J. Williams

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)545-560.e7
JournalDevelopmental cell
Volume53
Issue number5
DOIs
StatePublished - Jun 8 2020
Externally publishedYes

Keywords

  • ATAC-seq
  • axin
  • embryonic genome activation
  • mouse
  • post-transcriptional regulation
  • preimplantation embryo
  • tankyrase
  • WNT signaling pathway
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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