Extended Data Fig. 9. EP300 and partner transcription factors are important for zonal liver development.

a) Experimental timeline for testing role of EP300 in zonal liver development using Ad-shp300 (adenoviral vector for p300 shRNA, top). H&E stain for sections from rat liver injected with Ad-shSCR (adenoviral vector for scrambled shRNA, middle) and Ad-shp300 (adenoviral vector for p300 shRNA, bottom). Scale bar indicates 200 µm. (P: Portal vein, C: Central vein)

b) ICH stain for PROX1, ARG1, and GLUL of sections from rat liver injected with Ad-shSCR (adenoviral vector for scrambled shRNA, top) and Ad-shp300 (adenoviral vector for p300 shRNA, bottom). Scale bar indicates 200 µm. (P: Portal vein, C: Central vein)

c) RT-qPCR of ALB, ACSS2, ASL, CPS1, and OTC (zone 1) gene for Z1- and Z3-HLOs compared to freshly isolated PHH, H20 (20 um periportal hepatocytes) and H40 (40 um pericentral hepatocytes) (Data is mean ± SD, n = 9 independent experiments).

d) RT-qPCR of ALDH1A2, ALDH6A1, HIF1A, SREBF1, and GLUL (zone 3) gene for Z1- and Z3-HLOs compared to freshly isolated PHH, H20 (20 um periportal hepatocytes) and H40 (40 um pericentral hepatocytes) (Data is mean ± SD, n = 9 independent experiments).

e) EP300-TF ChIP-reChIP-PCR for H20 (20 um periportal hepatocytes) and H40 (40 um pericentral hepatocytes).

f) NR3C1-MECP2 ChIP-reChIP-qPCR for samples in (e). Data are mean ± SD, n = 9 independent experiments.