title: Genomic imprinting of the type 3 thyroid hormone deiodinase gene: regulation and developmental implications.
abstract: BACKGROUND
  In recent years, findings in a number of animal and human models have ignited renewed interest in the type 3 deiodinase (D3), the main enzyme responsible for the inactivation of thyroid hormones. The induction of D3 in models of illness and injury has raised critical questions about the physiological significance of reduced thyroid hormone availability in those states. Phenotypes in transgenic mice lacking this enzyme also point to important developmental roles for D3. A critical determinant of D3 expression is genomic imprinting, an epigenetic phenomenon that regulates a small number of dosage-critical genes in the mammalian genome. The D3 gene (Dio3) is imprinted and preferentially expressed from one of the alleles in most tissues.
  
  
  METHODS
  In the context of the physiological significance of D3 and the characteristics and purported origins of genomic imprinting, we review the current knowledge about the epigenetic mechanisms specifying gene dosage in the Dio3 locus.
  
  
  CONCLUSIONS
  Altered Dio3 dosage is detrimental to development, suggesting that the level of thyroid hormone action needs to be exquisitely tailored in a timely fashion to the requirements of particular tissues. An appropriate Dio3 dosage is the result of the coordinated action of certain genomic elements and epigenetic marks in the Dlk1-Dio3 domain.
  
  
  CONCLUSIONS
  The imprinting of Dio3 prompts intriguing questions about why the level of thyroid hormone signaling should be regulated in this rare epigenetic manner, and to what extent altered Dio3 expression due to aberrant imprinting may be implicated in human conditions. This article is part of a Special Issue entitled Thyroid hormone signalling.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Marika
authors.initials: M
authors.lastname: Charalambous
authors.forename: Arturo
authors.initials: A
authors.lastname: Hernandez
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D018392:Genomic Imprinting; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D013963:Thyroid Hormones; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase