Biology:Liver receptor homolog-1
 Generic protein structure example |
The liver receptor homolog-1 (LRH-1) also known as totipotency pioneer factor NR5A2 (nuclear receptor subfamily 5, group A, member 2) is a protein that in humans is encoded by the NR5A2 gene.[1][2] LRH-1 is a member of the nuclear receptor family of intracellular transcription factors.
LRH-1 plays a critical role in the regulation of development, cholesterol transport, bile acid homeostasis and steroidogenesis.[3][4][5][6]
LRH-1 is important for maintaining pluripotence of stem cells during embryonic development.[7][6]
Nr5a2 was recently identified at a totipotent pioneer factor.[6] The orphan nuclear receptor Nr5a2 has been shown to be important in fertility, ovarian function,[8] and zygotic genome activation (ZGA).[6] Heterozygosity for Nr5a2 is associated with reduced ovarian function, specifically in the synthesis of progesterone. This impaired progesterone production was associated with infertility in female mice, as well as increased incidence of pregnancy loss.[8] The loss of embryos around implantation associated with Nr5a2± mice indicated a possible interaction with genome-wide gene expression in early embryo development. Upon further investigation, Nr5a2 was found to regulate ZGA in mice embryos similar to that of Zelda in Drosophila. Nr5a2 is maternally contributed and regulates transcription activity in the early embryo by binding to distal cis-regulatory sequences and promoting chromatin accessibility. The change in chromatin conformation allows for the activation of transcription of about 72% of genes involved in ZGA.[6]
Interactions
Liver receptor homolog-1 has been shown to interact with the small heterodimer partner.[9][10]
References
- ↑ "Functional analysis of developmentally regulated chromatin-hypersensitive domains carrying the alpha 1-fetoprotein gene promoter and the albumin/alpha 1-fetoprotein intergenic enhancer". Molecular and Cellular Biology 13 (3): 1619–1633. March 1993. doi:10.1128/mcb.13.3.1619. PMID 7680097.
- ↑ "Assignment of the fetoprotein transcription factor gene (FTF) to human chromosome band 1q32.11 by in situ hybridization". Cytogenetics and Cell Genetics 82 (3–4): 269–270. 1998. doi:10.1159/000015116. PMID 9858833.
- ↑ "LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis". Trends in Cell Biology 14 (5): 250–260. May 2004. doi:10.1016/j.tcb.2004.03.008. PMID 15130581.
- ↑ "The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor". The Journal of Biological Chemistry 276 (27): 24767–24773. July 2001. doi:10.1074/jbc.M100912200. PMID 11331284.
- ↑ "CPF: an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7alpha-hydroxylase gene". Proceedings of the National Academy of Sciences of the United States of America 96 (12): 6660–6665. June 1999. doi:10.1073/pnas.96.12.6660. PMID 10359768. Bibcode: 1999PNAS...96.6660N.
- ↑ 6.0 6.1 6.2 6.3 6.4 "Zygotic genome activation by the totipotency pioneer factor Nr5a2". Science 378 (6626): 1305–1315. December 2022. doi:10.1126/science.abn7478. PMID 36423263. Bibcode: 2022Sci...378.1305G.
- ↑ "Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development". Molecular and Cellular Biology 25 (9): 3492–3505. May 2005. doi:10.1128/MCB.25.9.3492-3505.2005. PMID 15831456.
- ↑ 8.0 8.1 "Impaired progesterone production in Nr5a2± mice leads to a reduction in female reproductive function". Biology of Reproduction 77 (2): 217–225. August 2007. doi:10.1095/biolreprod.106.059121. PMID 17409375.
- ↑ "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology 16 (9): 2065–2076. September 2002. doi:10.1210/me.2001-0194. PMID 12198243.
- ↑ "Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner". The Journal of Biological Chemistry 277 (4): 2463–2467. January 2002. doi:10.1074/jbc.M105161200. PMID 11668176.
Further reading
- "Cloning and sequence analysis of the human gene encoding steroidogenic factor 1". Journal of Molecular Endocrinology 17 (2): 139–147. October 1996. doi:10.1677/jme.0.0170139. PMID 8938589.
- "Cloning and characterization of a novel human hepatocyte transcription factor, hB1F, which binds and activates enhancer II of hepatitis B virus". The Journal of Biological Chemistry 273 (44): 29022–29031. October 1998. doi:10.1074/jbc.273.44.29022. PMID 9786908.
- "A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis". Molecular Cell 6 (3): 517–526. September 2000. doi:10.1016/S1097-2765(00)00051-4. PMID 11030332.
- "Liver receptor homologue-1 is expressed in the adrenal and can regulate transcription of 11 beta-hydroxylase". Journal of Molecular Endocrinology 27 (2): 255–258. October 2001. doi:10.1677/jme.0.0270255. PMID 11564608.
- "Characterization of the genomic structure and tissue-specific promoter of the human nuclear receptor NR5A2 (hB1F) gene". Gene 273 (2): 239–249. August 2001. doi:10.1016/S0378-1119(01)00586-8. PMID 11595170.
- "Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes". The Journal of Biological Chemistry 277 (23): 20591–20597. June 2002. doi:10.1074/jbc.M201117200. PMID 11927588.
- "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Molecular Endocrinology 16 (6): 1367–1377. June 2002. doi:10.1210/mend.16.6.0843. PMID 12040021.
- "Liver receptor homologue-1 is expressed in human steroidogenic tissues and activates transcription of genes encoding steroidogenic enzymes". The Journal of Endocrinology 174 (3): R13–R17. September 2002. doi:10.1677/joe.0.174R013. PMID 12208674.
- "Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1". Molecular Cell 11 (6): 1575–1585. June 2003. doi:10.1016/S1097-2765(03)00236-3. PMID 12820970.
- "Activation incarnate". Developmental Cell 5 (1): 1–2. July 2003. doi:10.1016/S1534-5807(03)00196-5. PMID 12852843.
- "Liver receptor homolog 1 controls the expression of carboxyl ester lipase". The Journal of Biological Chemistry 278 (37): 35725–35731. September 2003. doi:10.1074/jbc.M302370200. PMID 12853459.
- "Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development". Molecular and Cellular Biology 23 (19): 6713–6724. October 2003. doi:10.1128/MCB.23.19.6713-6724.2003. PMID 12972592.
- "The role of the orphan nuclear receptor, liver receptor homologue-1, in the regulation of human corpus luteum 3beta-hydroxysteroid dehydrogenase type II". The Journal of Clinical Endocrinology and Metabolism 88 (12): 6020–6028. December 2003. doi:10.1210/jc.2003-030880. PMID 14671206.
- "LRH-1/hB1F and HNF1 synergistically up-regulate hepatitis B virus gene transcription and DNA replication". Cell Research 13 (6): 451–458. December 2003. doi:10.1038/sj.cr.7290187. PMID 14728801.
- "Liver receptor homolog-1 stimulates the progesterone biosynthetic pathway during follicle-stimulating hormone-induced granulosa cell differentiation". Endocrinology 145 (8): 3821–3829. August 2004. doi:10.1210/en.2004-0423. PMID 15117876.
External links
- NR5A2+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
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