title: Ectopic hbox12 Expression Evoked by Histone Deacetylase Inhibition Disrupts Axial Specification of the Sea Urchin Embryo.
abstract: Dorsal/ventral patterning of the sea urchin embryo depends upon the establishment of a Nodal-expressing ventral organizer. Recently, we showed that spatial positioning of this organizer relies on the dorsal-specific transcription of the Hbox12 repressor. Building on these findings, we determined the influence of the epigenetic milieu on the expression of hbox12 and nodal genes. We find that Trichostatin-A, a potent and selective histone-deacetylases inhibitor, induces histone hyperacetylation in hbox12 chromatin, evoking broad ectopic expression of the gene. Transcription of nodal concomitantly drops, prejudicing dorsal/ventral polarity of the resulting larvae. Remarkably, impairing hbox12 function, either in a spatially-restricted sector or in the whole embryo, specifically rescues nodal transcription in Trichostatin-A-treated larvae. Beyond strengthen the notion that nodal expression is not allowed in the presence of functional Hbox12 in the same cells, these results highlight a critical role of histone deacetylases in regulating the spatial expression of hbox12.
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Italy.|Mediterranean Center for Human Health Advanced Biotechnologies (CHAB), University of Palermo, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cavalieri
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Spinelli
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D019521:Body Patterning / Q000187:drug effects*; D002843:Chromatin / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012617:Sea Urchins / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D018398:Homeodomain Proteins; D006877:Hydroxamic Acids; D055457:Nodal Protein; C012589:trichostatin A; D006655:Histone Deacetylases