Hormone Response Elements (HREs) are specialized short DNA sequences that function as regulatory switches, modulating gene activity in response to specific hormones. These sequences enable hormones to initiate cellular and physiological changes. Notably, HREs exhibit positional and orientational flexibility within genes, allowing them to function regardless of their exact placement on the DNA.
The typical structure of a hormone response element (HRE) generally comprises two mirrored sequences (either inverted or direct repeats), which are separated by a span of three nucleotides. This configuration indicates that the receptor interacts with the HRE as a dimer.
HREs are classified into two categories: enhancers and silencers.
Mostly, HREs act as enhancers and are capable of functioning through heterologous promoters. This implies that when a specific HRE is positioned upstream of various promoters, it can still facilitate the activation of gene transcription.
Alternatively, HREs can also function as silencers, repressing gene transcription. These silencers typically exert their effect by binding to transcription factors, thereby inhibiting gene expression.
Hormonal Interaction with HREs:
Certain hormones, such as steroid or thyroid hormones, enter the cell, bind to their respective receptors, and subsequently interact directly with their corresponding HREs to regulate gene transcription.
In contrast, other hormones do not enter the cell but instead interact with cell surface receptors, which become activated. This activation triggers the production of secondary messengers, such as cyclic AMP or others. These messengers then translocate to the nucleus, where they bind to specific proteins. These proteins, in turn, bind to particular HREs on the DNA, activating or repressing gene expression.
Approach to Identifying HREs:
Researchers employ specific strategies to identify distinct HREs on DNA for various hormones. This involves constructing fusion genes by combining different gene segments, followed by an analysis of how particular DNA regions respond to different hormones. This approach enables the identification of HREs responsible for mediating the hormonal response.
Examples of HREs:
For every hormone, there’s a different HRE present in the DNA.
- Estrogen response element (ERE) for Estrogen Hormone.
- Thyroid hormone response element (TRE) for Thyroid Hormone.
- Vitamin D response element (VDRE) for Vitamin D Hormone.
- Androgen response element (ARE) for Androgen Hormone.
- Growth hormone response element (GHRE) for Growth Hormone.
- Glucocorticoid response element (GRE) for Glucocorticoid Hormone.
