Ectopic hbox12 Expression Evoked by Histone Deacetylase Inhibition Disrupts Axial Specification of the Sea Urchin Embryo

Vincenzo Cavalieri; Giovanni Spinelli

doi:10.1371/journal.pone.0143860

Ectopic hbox12 Expression Evoked by Histone Deacetylase Inhibition Disrupts Axial Specification of the Sea Urchin Embryo

PLoS One. 2015 Nov 30;10(11):e0143860. doi: 10.1371/journal.pone.0143860. eCollection 2015.

Authors

Vincenzo Cavalieri^{1

2}, Giovanni Spinelli¹

Affiliations

¹ Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Italy.
² Mediterranean Center for Human Health Advanced Biotechnologies (CHAB), University of Palermo, Italy.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation / drug effects
Animals
Body Patterning / drug effects*
Chromatin / drug effects
Embryo, Nonmammalian / metabolism
Gene Expression Regulation, Developmental
Histone Deacetylase Inhibitors / pharmacology*
Histone Deacetylases / metabolism*
Homeodomain Proteins / metabolism*
Hydroxamic Acids / pharmacology*
Nodal Protein / genetics
Nodal Protein / metabolism
Promoter Regions, Genetic / drug effects
Sea Urchins / embryology*
Sea Urchins / genetics
Sea Urchins / metabolism

Substances

Chromatin
Histone Deacetylase Inhibitors
Homeodomain Proteins
Hydroxamic Acids
Nodal Protein
trichostatin A
Histone Deacetylases

Grants and funding

This work was supported by the Università degli studi di Palermo - STEMBIO Award to VC, Università degli studi di Palermo - FFR ex60% to VC, Assessorato Regionale della Salute, Regione Siciliana - PO F.E.S.R. 4.1.1.1 RIMEDRI to VC and Assessorato Regionale della Salute, Regione Siciliana - PO F.E.S.R. 4.1.1.1 RIMEDRI to GS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.