Chronic administration of L-DOPA decreases the induction of H3K27me3S28p and alters the transcriptomal response to L-DOPA.

<p>A) L-DOPA increased H3S28p and H3K27me3S8p in the lesioned striatum that progressively decreased following subsequent administrations (H3S28p: lesion x day interaction: F_(2,25) = 38.17, p<0.0001; H3K27me3S28p: lesion x day interaction: F_(2,24) = 11.42, p = 0.0003). *** p<0.001, ** p<0.01, * p<0.05 vs unlesioned hemisphere of the same day. n = 3–6 per condition. Data are means ±S.E.M. B–D) Histograms of differentially expressed transcripts in lesioned striata after chronic L-DOPA compared to acute L-DOPA, from H3K27me3S28p positive and H3K27me3 positive genes (B), from H3K27me3S28p negative but H3K27me3 positive genes (C), and from genes regardless of specific histone marks (D). E) Venn-diagram showing number of genes induced exclusively by acute (53; subgroup a) or chronic (71; subgroup b) and genes commonly induced after both acute and chronic L-DOPA administration (43; subgroup c). F–H) mRNA levels of (F) <i>Ppm1n</i>, <i>Galr2</i>, (G) <i>Atf3</i>, <i>Klf4</i>, <i>Npas4</i>, (H) <i>Nurr1</i>, <i>Ngf</i>, <i>Lipg</i> relative to <i>Tbp</i> in unlesioned and lesioned striata of acutely or chronically saline or L-DOPA injected mice determined by RT-qPCR. n = 3 mice per condition, unlesioned and lesioned striata respectively. Data are means ±S.E.M of the biological triplicates. *** p<0.001, ** p<0.01, * p<0.05. Small letters a–c following the gene names in brackets in panel F–H refers to the subgroups in the Venn diagram in panel E.