New partners in regulation of gene expression: the enhancer of Trithorax and Polycomb Corto interacts with methylated ribosomal protein l12 via its chromodomain.
Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene expression. Over-expression of the Corto chromodomain (CortoCD) in transgenic flies shows that it is a chromatin-targeting module, critical for Corto function. Unexpectedly, mass spectrometry analysis reveals that polypeptides pulled down by CortoCD from nuclear extracts correspond to ribosomal proteins. Furthermore, real-time interaction analyses demonstrate that CortoCD binds with high affinity RPL12 tri-methylated on lysine 3. Corto and RPL12 co-localize with active epigenetic marks on polytene chromosomes, suggesting that both are involved in fine-tuning transcription of genes in open chromatin. RNA-seq based transcriptomes of wing imaginal discs over-expressing either CortoCD or RPL12 reveal that both factors deregulate large sets of common genes, which are enriched in heat-response and ribosomal protein genes, suggesting that they could be implicated in dynamic coordination of ribosome biogenesis. Chromatin immunoprecipitation experiments show that Corto and RPL12 bind hsp70 and are similarly recruited on gene body after heat shock. Hence, Corto and RPL12 could be involved together in regulation of gene transcription. We discuss whether pseudo-ribosomal complexes composed of various ribosomal proteins might participate in regulation of gene expression in connection with chromatin regulators.
Université Pierre et Marie Curie-Paris 6, UMR7622, Laboratoire de Biologie du Développement, Equipe Chromatine et Développement, Paris, France.
Anne
A
Coléno-Costes
Suk Min
SM
Jang
Augustin
A
de Vanssay
Julien
J
Rougeot
Tahar
T
Bouceba
Neel B
NB
Randsholt
Jean-Michel
JM
Gibert
Stéphane
S
Le Crom
Emmanuèle
E
Mouchel-Vielh
Sébastien
S
Bloyer
Frédérique
F
Peronnet
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D010641:Phenotype; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D059007:Polytene Chromosomes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014158:Transcription, Genetic; D059467:Transcriptome
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; C066770:Pc protein, Drosophila; D012269:Ribosomal Proteins; C110988:corto protein, Drosophila; C512571:trx protein, Drosophila; D063150:Polycomb Repressive Complex 1; D008239:Lysine