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Published on: November 26, 2013
Functional Definition of Thyroid Hormone Response Elements Based on a Synthetic STARR-seq Screen
Frédéric Flamant1, Yanis Zekri1, Romain Guyot1
1Institut de Génomique Fonctionnelle de Lyon, Université Claude Bernard Lyon I, CNRS UMR 5242, INRAE USC 1370 Ecole Normale Supérieure de Lyon, 69364 Lyon, France.
Abstract:
When bound to thyroid hormone, the nuclear receptor TRα1 activates the transcription of a number of genes in many cell types. It mainly acts by binding DNA as a heterodimer with retinoid X receptors at specific response elements related to the DR4 consensus sequence. However, the number of DR4-like elements in the genome exceed by far the number of occupied sites, indicating that minor variations in nucleotides composition deeply influence the DNA-binding capacity and transactivation activity of TRα1. An improved protocol of synthetic self-transcribing active regulatory region sequencing was used to quantitatively assess the transcriptional activity of thousands of synthetic sites in parallel. This functional screen highlights a strong correlation between the affinity of the heterodimers for DNA and their capacity to mediate the thyroid hormone response.
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