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Hormone response elements for the thyroid receptor-α include specific distal 5'-flanking DNA.
David P Lohry1, Taylor A Stevens1, Tongye Shen1
1Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN, USA.
Science Advances
|November 27, 2024
Summary
Conserved DNA sequences interact with thyroid receptor-α (TRα) to regulate gene transcription. These interactions distort DNA structure, challenging current definitions of hormone response elements (HREs).
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Gene transcription relies on precise interactions between transcription factors and DNA.
- The role of distal DNA sequences in regulating transcription factor activity is not fully understood.
Purpose of the Study:
- To investigate the interaction between 5'-flanking DNA sequences and the thyroid receptor-α (TRα).
- To elucidate the mechanism by which these interactions control transcriptional activity.
Main Methods:
- Simulated modeling and dynamics
- Chromatin immunoprecipitation sequencing (ChIP-seq)
- Atomic force microscopy (AFM)
- Reporter gene assays
Main Results:
- Conserved 5'-flanking sequences directly interact with the intrinsically disordered amino-terminal region of TRα.
- Specific lysine/arginine-DNA minor groove interactions were identified, leading to DNA structural distortions.
- Reporter gene assays confirmed the importance of these distal sequences in transcriptional regulation.
Conclusions:
- Current definitions of DNA hormone response elements (HREs) are inadequate.
- Future HRE descriptions should include conserved distal DNA sequences.
- Lysine/arginine-rich motifs in intrinsically disordered regions of nuclear receptors are crucial for transcriptional control.
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