Chromodomains are conserved domains found in many regulators of chromatin structure. Most of them recognize methylated lysine on histone tails. The Drosophila melanogaster Enhancer o f Polycomb and Trithorax Corto that is involved in both silencing and activation of gene expression bears a chromodomain (CortoCD). Overexpression of CortoCD in transgenic flies shows that it behaves as a chromatin-targeting module. Mass spectrometry analysis of peptides pulled-down by CortoCD from nuclear extracts reveals that they correspond to nuclear ribosomal proteins (RPs). Among them, I focused on RPL12 since homologues of this RP have been shown to be methylated in several species. CortoCD binds with high affinity RPL12 trimethylated on lysine 3 (RPL12K3me3) as demonstrated by real-time interaction analyses. Co-localization of Corto and RPL12 with active epigenetic marks on polytene chromosomes suggests that they are involved in finetuning transcription of genes located in open chromatin. Analysis of two Corto and RPL12 transcriptional targets by ChIP (Chromatin Immuno Precipitation) shows that both proteins are not enriched at promoters but rather located in the core region of these genes. Altogether, our results suggest a role for Corto and RPL12 in transcriptional elongation. RNAseq analyses of wing imaginal discs overexpressing either Corto or RPL12 show that most deregulated genes are shared by both factors. Interestingly, RP genes are among these common targets suggesting that Corto and RPL12 are involved in dynamic coordination of ribosome biogenesis. Our results show for the first time that an RP and a chromatin regulator can cooperate in the control of gene expression.
