An essential role of histone deacetylases in postembryonic organ transformations in Xenopus laevis

Amphibian metamorphosis is the result of thyroid hormone (TH)-induced organ transformations including de novo morphogenesis, tissue remodeling and res orption through programmed cell death (apoptosis). All chances during metam orphosis are presumed to be mediated through gene regulation cascades initi ated by TH. Numerous studies have implicated important roles of chromatin r emodeling in transcriptional regulation. In particular, several lines of ev idence support the view that histone acetylation is associated with transcr iptional activation and histone deacetylation leads to gene repression. Her e we address the physiological roles of histone deacetylases during vertebr ate postembryonic development by using amphibian metamorphosis as a model. We first demonstrate that Xenopus laevis Rpd3 (a histone deacetylase) and S in3 (a corepressor associated to Rpd3) are expressed in premetamorphic and metamorphic tadpole tissues, suggesting their involvement in these postembr yonic processes. To test this possibility, we use a histone deacetylase inh ibitor, trichostatin A, to block histone deacetylases and examine the devel opment of the tadpoles. Our results indicate both natural and T,-induced me tamorphosis are blocked by the inhibitor. We further show that this drug in hibits metamorphosis in different tissues, whether they involve de novo dev elopment or resorption through apoptosis, and that it functions in a stage- dependent but organ-autonomous manner. The data thus support an important r ole of histone deacetylases in the gene regulation cascades induced by T-3 during metamorphosis.