BUSCADOR RECOLECTA

The N-terminal tails of eukaryotic histones are frequently posttranslationally modified. The role of these modifications in transcriptional regulation is well-documented. However, the extent to which the enzymatic processes of histone posttranslational modification might affect metabolic regulation is less clear. Here, we investigated how histone methylation might affect metabolism using metabolomics, proteomics, and RNA-seq data from cancer cell lines, primary tumour samples and healthy tissue samples. In cancer, the expression of histone methyltransferases (HMTs) was inversely correlated to the activity of NNMT, an enzyme previously characterised as a methyl sink that disposes of excess methyl groups carried by the universal methyl donor S-adenosyl methionine (SAM or AdoMet). In healthy tissues, histone methylation was inversely correlated to the levels of an alternative methyl sink, PEMT. These associations affected the levels of multiple histone marks on chromatin genome-wide but had no detectable impact on transcriptional regulation. We show that HMTs with a variety of different associations to transcription are co-regulated by the Retinoblastoma (Rb) tumour suppressor in human cells. Rb-mutant cancers show increased total HMT activity and down-regulation of NNMT. Together, our results suggest that the total activity of HMTs affects SAM metabolism, independent of transcriptional regulation., Peer reviewed

GTEx PEMT-HMT correlation all tissues full labelled plots., Peer reviewed

GTEx NNMT-HMT correlation all tissues full labelled plots., Peer reviewed

TCGA NNMT-HMT correlation all cancers full labelled plots., Peer reviewed

CCLE NNMT-HMT correlation all cancers full labelled plots., Peer reviewed

Contents: S1 Geographical description of the German Part of the Elbe River basin – S1.-- S2 Drought indices – S9.-- S3 Aspects of the socio-economic drought impacts – S13.-- References, Peer reviewed

Subcellular localisations of transsulphuration and glutathione synthesis genes., Peer reviewed

Supplementary Figures (1-2) and Tables (1-3)., Peer reviewed

Table S1. Statistics of the co-registration statistics between the external DEMs and the ICESat-2 snow-off DEM.-- Table S2. Statistics of the snow depth residuals for different snow-off Digital Elevation Models (DEMs) on 12 March 2019. The ICESat-2-ASO product is shown in detail on Figure 3. All residuals are shown in Figure 5 and S4.-- Table S3. Statistics of the co-registration statistics between the Pléiades and Copernicus DEMs to the ASO DEM at15 m. All these DEMs were previously co-registered to the ICESat-2 snow-off points.-- Figure S1. Map of the mean annual snow cover duration in the upper Tuolumne basin calculated from a time series of MODIS images (MOD10A1).-- Figure S2. Optimization of the kappa index to determine the photon count threshold defining snow-on and snow-off points based on MODIS snow cover area data.-- Figure S3. Vertical uncertainty of the ATL06 elevation (sigma_h_mean) against along-track slope (dh_fit_dx). The along-track slope (dh_fit_dx) is directly provided in ATL06.-- Figure S4. Same figure as Figure 5 but with snow depth derived from ICESat-2 and the ASO DEM (green, identical to Fig. 5) and ICESat-2 and the Copernicus DEM (purple). Note the different y-scale compared to Figure 5.-- Figure S5. Same as Figure 5 but selecting ICESat-2 ATL06 snow-on points of the strong beams only.-- Figure S6. Same as Figure 5 but selecting ICESat-2 ATL06 snow-on points of the weak beams only.-- Figure S7. Same as Figure 5 but calculating the relative snow depth error (ICESat-2 derived snow depth minus ASO snow depth divided by ASO snow depth) rather than the absolute snow depth error (ICESat-2 derived snow depth minus ASO snow depth).-- Figure S8. Distribution of the snow-off residual (ICESat-2 minus DEM) before (black line) and after coregistration (color) for the ASO DTM (left), the Pléiades DEM (middle) and the Copernicus DEM (right). The vertical lines show the median plus/minus the NMAD after coregistration.-- Figure S9. Snow depth (colored boxes) and snow-off (white boxes) residuals for ICESat-2 – ASO (left) and ICESat-2 – Pléiades (right). Transparent boxplots show the data where less than 100 points were available.-- Figure S10. Elevation difference of the snow-off DEMs, the difference between the Copernicus 30 DEM and the ASO DEM (a) and the Pléiades DEM and the ASO DEM (b). All DEMs were individually co-registered on the ICESat-2 snow-off points. © Author(s) 2023. CC BY 4.0 License. The copyright of individual parts of the supplement might differ from the article licence., Peer reviewed

This PDF file includes: Supplementary Fig. 1 to 5 and Supplementary Table 1., Peer reviewed