bile acid nuclear receptor activity

Definition

Target type: molecularfunction

A DNA-binding transcription factor activity regulated by binding to a bile acid that modulates the transcription of specific gene sets transcribed by RNA polymerase II. [GOC:bf, PMID:12016314]

Bile acid nuclear receptors (BARs) are members of the nuclear receptor superfamily that play a crucial role in regulating lipid and glucose metabolism, as well as inflammation and bile acid homeostasis. These receptors function as ligand-activated transcription factors, binding to specific DNA sequences called bile acid response elements (BAREs) in the promoter regions of target genes. Upon binding of bile acids, BARs undergo conformational changes that allow them to recruit coactivator proteins, leading to the transcriptional activation of their target genes. The molecular functions of BARs are multifaceted and involve several steps:

1. **Ligand Binding:** BARs exhibit high affinity for bile acids, which act as endogenous ligands. The binding of bile acids to the ligand-binding domain of BARs initiates a cascade of events that ultimately result in gene regulation.

2. **Conformational Changes:** Upon ligand binding, BARs undergo significant conformational changes. This involves a shift in the receptor's structure, leading to the exposure of the activation function (AF) domain.

3. **Coactivator Recruitment:** The exposed AF domain interacts with coactivator proteins, which are essential for transcriptional activation. Coactivators possess intrinsic enzymatic activities, such as histone acetyltransferase (HAT) or histone methyltransferase (HMT) activity, which modify chromatin structure and promote gene expression.

4. **DNA Binding:** BARs bind to specific DNA sequences known as BAREs located in the promoter regions of target genes. The binding of BARs to BAREs is crucial for the regulation of gene expression.

5. **Transcriptional Activation:** Through a complex interplay of ligand binding, conformational changes, coactivator recruitment, and DNA binding, BARs ultimately regulate the transcription of target genes. This transcriptional regulation plays a critical role in maintaining lipid and glucose homeostasis, modulating inflammation, and controlling bile acid metabolism.

BARs are involved in various physiological processes, including:

* **Regulation of Lipid Metabolism:** BARs regulate the expression of genes involved in lipid metabolism, such as lipogenesis, lipolysis, and cholesterol synthesis.

* **Regulation of Glucose Metabolism:** BARs influence glucose metabolism by affecting the expression of genes involved in insulin sensitivity and glucose uptake.

* **Bile Acid Homeostasis:** BARs play a crucial role in regulating bile acid synthesis, transport, and detoxification. They contribute to the maintenance of bile acid levels within a physiological range.

* **Inflammation Modulation:** BARs are implicated in the modulation of inflammation by influencing the expression of inflammatory mediators.

In summary, the molecular function of bile acid nuclear receptor activity involves a complex interplay of ligand binding, conformational changes, coactivator recruitment, DNA binding, and transcriptional activation. This intricate process plays a vital role in regulating lipid and glucose metabolism, maintaining bile acid homeostasis, and modulating inflammation.'
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Proteins (1)

Compounds (29)