Functional Definition of Thyroid Hormone Response Elements Based on a Synthetic STARR-seq Screen - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Endocrinology Year : 2022

Functional Definition of Thyroid Hormone Response Elements Based on a Synthetic STARR-seq Screen

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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hal-03746531 , version 1 (05-08-2022)

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Frédéric Flamant, Yanis Zekri, Romain Guyot. Functional Definition of Thyroid Hormone Response Elements Based on a Synthetic STARR-seq Screen. Endocrinology, 2022, 163 (8), pp.bqac084. ⟨10.1210/endocr/bqac084⟩. ⟨hal-03746531⟩
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