Epigenetic control of type 2 and 3 deiodinases in myogenesis: role of Lysine-specific Demethylase enzyme and FoxO3
Open Access
- 8 February 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 41 (6), 3551-3562
- https://doi.org/10.1093/nar/gkt065
Abstract
The proliferation and differentiation of muscle precursor cells require myogenic regulatory factors and chromatin modifiers whose concerted action dynamically regulates access to DNA and allows reprogramming of cells towards terminal differentiation. Type 2 deiodinase (D2), the thyroid hormone (TH)-activating enzyme, is sharply upregulated during myoblast differentiation, whereas type 3 deiodinase (D3), the TH-inactivating enzyme, is downregulated. The molecular determinants controlling synchronized D2 and D3 expression in muscle differentiation are completely unknown. Here, we report that the histone H3 demethylating enzyme (LSD-1) is essential for transcriptional induction of D2 and repression of D3. LSD-1 relieves the repressive marks (H3-K9me2-3) on the Dio2 promoter and the activation marks (H3-K4me2-3) on the Dio3 promoter. LSD-1 silencing impairs the D2 surge in skeletal muscle differentiation while inducing D3 expression thereby leading to a global decrease in intracellular TH production. Furthermore, endogenous LSD-1 interacts with FoxO3a, and abrogation of FoxO3-DNA binding compromises the ability of LSD-1 to induce D2. Our data reveal a novel epigenetic control of reciprocal deiodinases expression and provide a molecular mechanism by which LSD-1, through the opposite regulation of D2 and D3 expression, acts as a molecular switch that dynamically finely tunes the cellular needs of active TH during myogenesis.Keywords
This publication has 39 references indexed in Scilit:
- Structural Basis of LSD1-CoREST Selectivity in Histone H3 RecognitionJournal of Biological Chemistry, 2007
- PLU-1 Is an H3K4 Demethylase Involved in Transcriptional Repression and Breast Cancer Cell ProliferationMolecular Cell, 2007
- The Small Polyphenolic Molecule Kaempferol Increases Cellular Energy Expenditure and Thyroid Hormone ActivationDiabetes, 2007
- MyoD and the transcriptional control of myogenesisSeminars in Cell & Developmental Biology, 2005
- Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1Cell, 2004
- Deacetylase Inhibitors Increase Muscle Cell Size by Promoting Myoblast Recruitment and Fusion through Induction of FollistatinDevelopmental Cell, 2004
- Sir2 Regulates Skeletal Muscle Differentiation as a Potential Sensor of the Redox StateMolecular Cell, 2003
- ALL-1 Is a Histone Methyltransferase that Assembles a Supercomplex of Proteins Involved in Transcriptional RegulationMolecular Cell, 2002
- HDAC4 deacetylase associates with and represses the MEF2 transcription factorThe EMBO Journal, 1999
- Clinical observations on thyrotoxicosis coexisting with myotonic dystrophy.1976