NR5A2
Description
The NR5A2 (nuclear receptor subfamily 5 group A member 2) is a protein-coding gene located on chromosome 1.
NR5A2, also known as Liver Receptor Homolog-1 (LRH-1), is a protein encoded by the NR5A2 gene in humans. It belongs to the nuclear receptor family of intracellular transcription factors and plays a vital role in development, cholesterol transport, bile acid homeostasis, and steroidogenesis. NR5A2 is crucial for maintaining pluripotency in stem cells during embryonic development. Recent research has identified NR5A2 as a totipotent pioneer factor. This orphan nuclear receptor has been implicated in fertility, ovarian function, and zygotic genome activation (ZGA). Heterozygosity for NR5A2 is associated with reduced ovarian function, particularly in progesterone synthesis, leading to infertility in female mice and increased pregnancy loss. The loss of embryos around implantation in Nr5a2+/- mice suggests an interaction with genome-wide gene expression in early embryo development. Further investigation has revealed that NR5A2 regulates ZGA in mouse embryos, similar to the role of Zelda in Drosophila.
NR5A2, also known as Liver Receptor Homolog-1 (LRH-1), plays a crucial role in regulating lipid metabolism, particularly in bile acid synthesis, cholesterol homeostasis, and triglyceride synthesis. It acts as a key metabolic sensor by controlling the expression of genes involved in these processes. NR5A2, in collaboration with oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, serves as an essential transcriptional regulator of lipid metabolism. Furthermore, NR5A2 exhibits anti-inflammatory properties during the hepatic acute phase response by functioning as a corepressor. This role involves preventing the dissociation of the N-Cor corepressor complex, ultimately inhibiting the hepatic acute phase response. NR5A2 may also be responsible for the liver-specific activity of enhancer II, likely in conjunction with other hepatocyte transcription factors. Notably, NR5A2 is a key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in the liver. It might also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. Additionally, NR5A2 activates the transcription of CYP2C38.
NR5A2 is also known as B1F, B1F2, CPF, FTF, FTZ-F1, FTZ-F1beta, LRH-1, LRH1, hB1F-2.
