Fig. 10: Model of Tet1s and Tet1 regulation during the cell cycle. | Nature Communications

Fig. 10: Model of Tet1s and Tet1 regulation during the cell cycle.

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

Fig. 10

Tet1 via its zinc finger domain is tethered away from heterochromatin, which prevents spreading of hydroxymethylation to these regions. The short isoform Tet1s lacking this domain gets ubiquitinated by the CRL4(VprBP) complex and the modified protein is bound by Uhrf1 and recruited to late-replicating heterochromatin. This targets Tet1s activity to heterochromatin and results in aberrant oxidation of methylcytosine in heterochromatic regions in both human and mouse cells depending on the level of this isoform. This in turn also results in the reactivation of silenced repetitive DNA elements like LINE 1 or major satellite repeats.

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