Extended Data Fig. 6: TEAD4 interacts with TET1 through its YAP binding domain (YBD).

a, Co-IP assay showing physical interactions between TET1 and RUNX1 or TEAD1/TEAD4. The indicated constructs were transfected into HEK293T cells, lysed and subjected to immunoprecipitation assays. Normal IgG immunoprecipitates serve as negative control. b, Co-IP assay showing no interactions between TET1 and YAP. Co-IP assay was conducted under same condition as in (a). c, Co-IP assay showing physical interactions between TET1 and RUNX1 or TEAD1/TEAD4 in the presence or absence of DNA/RNA nuclease. The indicated constructs were transfected into HEK293T cells, lysed with or without benzonase treatment before immunoprecipitation assays. Note the co-IP between TET1 and RUNX1 or TEAD1/TEAD4, regardless of nuclease treatment. d, Co-IP assay showing physical interactions between TET1 and TEAD1/TEAD4. Note that the TET1-TEAD1/TEAD4 interaction were abolished by deletion of the CXXC domain in TET1 protein. e, Co-IP assay showing physical interactions between TEAD4 and TET1. The schematic diagram indicates the TEAD4 mutants used: TEAD4ΔΤΕΑ is defective in DNA-binding and TEAD4-Y429H is defective in YAP-binding. Both TEAD4 mutants interacted with TET1. f, Co-IP assay showing physical interactions between TEAD4 and TET1. Note that TEAD4 interacts with TET1 through its YAP binding domain (YBD). g, Co-IP assay showing physical interactions between TEAD4 and TET1/2/3. Note the co-IP between TEAD4 and TET1, not TET2 or TET3. h, Co-IP assay showing physical interactions between endogenous TET1 and TEAD1 in YAPTg livers. i, Genome track showing Tet1 RNA-seq in YAPTg livers. j, TET1 exon usage profile in LIHC samples from the TCGA database. Exon usage profile was visualized with TSVdb web tool. Patients are represents in x-axis and exon usage of each exon are showed in y-axis. Images are representative of two (a, b, c, g) or three (d, e, f, h) independent experiments.