Biology Reference
In-Depth Information
CHAPTER TEN
Unliganded Thyroid Hormone
Receptor Regulates Metamorphic
Timing via the Recruitment of
Histone Deacetylase Complexes
Yun-Bo Shi
1
Section on Molecular Morphogenesis, Program in Cellular Regulation and Metabolism, NICHD, NIH,
Bethesda, Maryland, USA
1
Corresponding author: e-mail address: Shi@helix.nih.gov
Contents
1.
Introduction
276
2. TR Function During Frog Development
279
3. Unliganded TR Recruits Corepressor Complexes to Control Metamorphic Timing
282
4. Coactivator Recruitment for Metamorphic Progression
285
5. Temporal Regulation of Organ-Specific Metamorphosis
285
6. Conclusions
291
Acknowledgment
291
References
291
Abstract
Anuran metamorphosis involves a complex series of tissue transformations that change
an aquatic tadpole to a terrestrial frog and resembles the postembryonic perinatal
period in mammals. Thyroid hormone (TH) plays a causative role in amphibian meta-
morphosis and its effect is mediated by TH receptors (TRs). Molecular analyses during
Xenopus development have shown that unliganded TR recruits histone deacetylase
(HDAC)-containing N-CoR/SMRT complexes and causes histone deacetylation at target
genes while liganded TR leads to increased histone acetylations and altered histone
methylations at target genes. Transgenic studies involving mutant TR-cofactors have
shown that corepressor recruitment by unliganded TR is required to ensure proper
timing of the onset of metamorphosis while coactivator levels influence the rate of
metamorphic progression. In addition, a number of factors that can influence cellular
free TH levels appear to contribute the timing of metamorphic transformations of dif-
ferent organs by regulating the levels of unliganded vs. liganded TR in an organ-specific
manner. Thus, the recruitment of HDAC-containing corepressor complexes by
unliganded TR likely controls both the timing of the initiation of metamorphosis and
the temporal regulation of organ-specific transformations. Similar mechanisms likely
mediate TR function in mammals as the maturation of many organs during
