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. 2020 Oct 2;11:4956. doi: 10.1038/s41467-020-18729-6

Fig. 7. Model of Tet-mediated 5hmC as a mark of transcriptome flexibility in ESCs.

Fig. 7

a Scheme illustrating that spontaneous ESC-to-EB differentiation leads to reduced Tet1 and Tet2 expression and to a marked decrease in 5hmC. b 5hmC mRNA modification acts as an essential regulatory layer to safeguard efficient, timely, authentic downregulation of lineage-specific genes. 1. In WT ESCs, Tet1 and Tet2 hydroxymethylate many RNA transcripts, such as those encoding key pluripotency-related regulators (e.g. Eed, Jarid2). 2. 5hmC results in transcript destabilization. 3. This leads to an appropriate expression level (not too high, not too low) of these key cell fate determinants. 4. Consequently, this would ensure adequate repression of lineage-specific factors. 5. This controlled repression critically prepares ESCs to rapidly respond to external cues. 6. This stepwise model would ensure orderly differentiation of ESCs to EBs.