Fig. 5.

Chemical inhibition of histone demethylase activity leads to the disruption of normal gene expression in gametocytes a Expression profiles (log₂Cy5/Cy3) of genes encoding the P. falciparum Jumonji-C domain-containing demethylases (jmjc1, jmjc2 and jmj3) and the H3K36-specific methyltransferase, set2 on days 0 to 7 of gametocyte (GC) development [36], with the grey shadowed region representing days of increased transcript abundance of the demethylases that are associated with stage II gametocytes. b H3K36me2&3 abundance on day 4 of gametocyte development following treatment (24 h, 5 µM) with the Jumonji demethylase inhibitors JIB-04, ML324 or GSK-J4 or the lysine specific demethylase 1 (LSD1) inhibitor 2-PCPA expressed as fold changes (treated/parallel untreated control gametocytes) of relative density units (RDU). c Functional classification of differentially expressed genes (log₂ fold change ≥ 0.5 in either direction) with decreased (blue) or increased (red) transcript abundance in response to the inhibition of histone demethylase activity by JIB-04. The % of differentially expressed genes assigned to each biological category is shown. The proportion (%) of differentially expressed genes s that had H3K36me2/3 occupancy (light grey) or enrichment (dark grey) in the stage II gametocytes (data representative of two independent biological repeats) are shown on the two inner most segments. Transcript levels in the untreated and JIB-04 treated gametocytes are exemplified for certain differentially expressed genes. d Comparison of differentially expressed genes (blue and pink) in gametocytes (GC) treated with JIB-04 in this study with differentially expressed genes in JIB-04 treated asexual parasites (shown in grey, [38]), immature gametocytes (imGC) treated with the G9a-specific inhibitor BIX-0129 [69] and imGC treated with the HDAC inhibitor Trichostatin A [70]. Full descriptions of gene names and their PlasmoDB IDs are available in Additional file 2: Table S4