Research Paper Volume 10, Issue 6 pp 1223—1238

Figure 7. ATRX is required for the transcription of several thyroid hormone responsive genes in the liver. In the control, T4 is bound to thyroxine binding globulin (TBG) in the blood. It is converted to T3 in the liver by Dio1. Both T4 and T3 can be inactivated by Dio3 to produce the inactive molecules T2 and rT3. T3 binds its receptor Thrβ (found as a heterodimer with retinoid x receptor), which enters the nucleus, binds a thyroid hormone responsive element and initiates transcription. In Atrx Foxg1cre mice there is an increase in TBG and a decrease in T4 in the serum. In the liver, there is a decrease in Dio1 and an increase in Dio3. Any T4 present is likely converted to rT3. Low levels of Thrβ acts as a transcriptional repressor. Following treatment with T4 in Atrx Foxg1cre mice, there are control levels of TBG and T4 in the blood. In the liver, Dio1 is at control levels and Dio3 is repressed. T4 is converted to T3 where it binds its receptor and transcription occurs normally. This occurs for a subset of genes (Dio1, Dio3 and Thrβ). However, some genes (Igf1, Prlr, Ghr and Thrsp) are still transcriptionally repressed following T4 treatment. This suggests that ATRX is required for the transcription of some thyroid hormone responsive genes.