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Fig. 3 | Clinical Epigenetics

Fig. 3

From: Regulating role of fetal thyroid hormones on placental mitochondrial DNA methylation: epidemiological evidence from the ENVIRONAGE birth cohort study

Fig. 3

Simplified scheme of T3-dependent mitochondrial biogenesis through coordinated regulation of nuclear and mitochondrial gene products. T3 binds to thyroid receptors (TRs) (1) which consecutively bind to response elements in the nucleus activating expression of mitochondrial-related genes such as PPARGC1A (2). Alternatively, specific TRs are localized in the mitochondrial matrix (p43). The T3-p43 complex binds to response elements in the mitochondrial genome, of which two elements are located in the D-loop and one in the 12S rRNA (MT-RNR1) gene (3). We suggest that methylation of the mtDNA genome, in particular in the D-loop and MT-RNR1 region, could intervene with T3-dependent mitochondrial protein production through conformational or structural changes making the mtDNA less accessible to proteins and transcription factors such as the T3-dependent transcription factor p43 (4)

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