Extended Data Fig. 10: Dietary valine restriction inhibits colon cancer progression and DNA damage dependent on the activity of TET2.
From: Human HDAC6 senses valine abundancy to regulate DNA damage
a,b, Images (a) and quantification for γH2AX (b) with immunofluorescence staining for γH2AX (red) and PAR (green) of tumour sections in the prevention group in Fig. 5b. Scale bar, 10 μm. c,d, Representative images (c) and quantification for γH2AX (d) with immune-fluorescence staining for γH2AX (red) and PAR (green) of tumour sections in the treatment group in Fig. 5d. Scale bar, 10 μm. e,f, Representative images (e) and quantification for γH2AX (f) with immunofluorescence staining for γH2AX (red) and PAR (green) of tumour sections in 5 f. Scale bar, 10 μm. g,h, Representative images (g) and quantification for γH2AX (h) with immunofluorescence staining for γH2AX (red) and PAR (green) of tumour sections in 5 h. Scale bar, 10 μm. i, Tumour volume of nude mice inoculated with TET2 WT, TET2 knockdown HCT116 cells infected with TET2 WT or mutant virus fed on 0.82% or 0.41% valine diet. j,k, Tumour images (j) and weight (k) at the end point from i. l, Body weight of nude mice in i. m, n, Representative images (m) and quantification for γH2AX (n) with immunofluorescence staining for γH2AX (red) and PAR (green) of tumour sections in j. Scale bar, 10 μm. o, Immunostaining of tumour sections for 5hmC (red) and nuclei (blue) from j. Scale bar, 10 μm. p, Illustration of the proposed mechanism of HDAC6 sensing valine deprivation via the ___domain of SE14 dictating the epigenetic modification of 5hmC. For b, f, h, n, n = 100 microscopic views examined for 6 mice. For d, n = 101 microscopic views examined for 6 mice. For i, k and l, n = 7 mice. Data are presented as mean ± s.d.. Statistical analysis was performed using Mann–Whitney U-test (b, d, f, h, n), one-way ANOVA (i, l, k) and two-way ANOVA (k); *P < 0.05, **P < 0.01, ***P < 0.001, NS, not significant. Schematic in p was created using BioRender (https://BioRender.com). For gel source data, see Supplementary Fig. 1.
