Nature Communications (Sep 2022)

Isoform-specific and ubiquitination dependent recruitment of Tet1 to replicating heterochromatin modulates methylcytosine oxidation

  • María Arroyo,
  • Florian D. Hastert,
  • Andreas Zhadan,
  • Florian Schelter,
  • Susanne Zimbelmann,
  • Cathia Rausch,
  • Anne K. Ludwig,
  • Thomas Carell,
  • M. Cristina Cardoso

DOI
https://doi.org/10.1038/s41467-022-32799-8
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 28

Abstract

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A short isoform of the Tet1 enzyme (Tet1s) that oxidizes the DNA 5-methylcytosine (5mC) mark is overexpressed in tumors. Here the authors show Tet1s, but not full length Tet1, changes localization over the cell cycle upon ubiquitination and Uhrf1 interaction and is targeted to heterochromatin during S-phase. This leads to 5mC oxidation and loss of DNA methylation in heterochromatin.