Hormone response elements for the thyroid receptor-α include specific distal 5′-flanking DNA

• DOI: 10.1126/sciadv.adr1033
• Publication Date: 2024-11-27T19:01:25Z
• Authors: David P. Lohry; Taylor A. Stevens; Tongye Shen; Elias J. Fernandez
• Keywords: Hormone response element; Response element; Transcription

Optimal gene transcription is achieved through precise interactions between factors and their DNA binding sites. We provide evidence that conserved distally located 5′-flanking sequences interact directly with the intrinsically disordered amino-terminal region of thyroid receptor-α (TRα) to control transcriptional activity. Simulated modeling dynamics multiple ChIP-seq–derived consistently reveal specific lysine/arginine–DNA minor groove interactions. The impact these distort structural conformations, are also revealed atomic force microscopy. importance further emphasized reporter assays comparisons canonical response elements. Overall, study reveals inadequacy current definitions hormone element (HRE) suggests future descriptions HRE include distal sequences. broad this underscored by common occurrence Lys/Arg-rich motifs within regions nuclear receptors.