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

ABSTRACT: Optimal gene transcription is achieved through precise interactions between transcription 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 the thyroid receptor-α (TRα) to control transcriptional activity. Simulated modeling and dynamics with multiple ChIP-seq-derived sequences consistently reveal specific lysine/arginine-DNA minor groove interactions. The impact of these interactions is to distort DNA structural conformations, and these are also revealed with atomic force microscopy. The importance of the 5'-flanking DNA is further emphasized with reporter gene assays and comparisons with canonical response elements. Overall, the study reveals the inade

SUBMITTER: Lohry DP 

PROVIDER: S-EPMC11601197 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature