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Liver receptor homolog-1

From Wikipedia, the free encyclopedia

NR5A2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNR5A2, B1F, B1F2, CPF, FTF, FTZ-F1, FTZ-F1beta, LRH-1, LRH1, hB1F-2, nuclear receptor subfamily 5 group A member 2
External IDsOMIM: 604453; MGI: 1346834; HomoloGene: 20827; GeneCards: NR5A2; OMA:NR5A2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2494

26424

Ensembl

ENSG00000116833

ENSMUSG00000026398

UniProt

O00482

P45448

RefSeq (mRNA)

NM_001276464
NM_003822
NM_205860

NM_001159769
NM_030676

RefSeq (protein)

NP_001263393
NP_003813
NP_995582

NP_001153241
NP_109601

Location (UCSC)Chr 1: 200.03 – 200.18 MbChr 1: 136.77 – 136.89 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6] 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.[7][8][9][10]

LRH-1 is important for maintaining pluripotence of stem cells during embryonic development.[11][10]

Nr5a2 was recently identified at a totipotent pioneer factor.[10] The orphan nuclear receptor Nr5a2 has been shown to be important in fertility, ovarian function,[12] and zygotic genome activation (ZGA).[10] 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.[12] 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.[10]

Interactions

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Liver receptor homolog-1 has been shown to interact with the small heterodimer partner.[13][14]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000116833 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026398 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Bernier D, Thomassin H, Allard D, Guertin M, Hamel D, Blaquière M, et al. (March 1993). "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. doi:10.1128/mcb.13.3.1619. PMC 359474. PMID 7680097.
  6. ^ Galarneau L, Drouin R, Bélanger L (1998). "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. doi:10.1159/000015116. PMID 9858833. S2CID 46813832.
  7. ^ Fayard E, Auwerx J, Schoonjans K (May 2004). "LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis". Trends in Cell Biology. 14 (5): 250–260. doi:10.1016/j.tcb.2004.03.008. PMID 15130581.
  8. ^ Luo Y, Liang CP, Tall AR (July 2001). "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. doi:10.1074/jbc.M100912200. PMID 11331284.
  9. ^ Nitta M, Ku S, Brown C, Okamoto AY, Shan B (June 1999). "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. Bibcode:1999PNAS...96.6660N. doi:10.1073/pnas.96.12.6660. PMC 21971. PMID 10359768.
  10. ^ a b c d e Gassler J, Kobayashi W, Gáspár I, Ruangroengkulrith S, Mohanan A, Gómez Hernández L, et al. (December 2022). "Zygotic genome activation by the totipotency pioneer factor Nr5a2". Science. 378 (6626): 1305–1315. Bibcode:2022Sci...378.1305G. doi:10.1126/science.abn7478. PMID 36423263. S2CID 248923539.
  11. ^ Gu P, Goodwin B, Chung AC, Xu X, Wheeler DA, Price RR, et al. (May 2005). "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. doi:10.1128/MCB.25.9.3492-3505.2005. PMC 1084298. PMID 15831456.
  12. ^ a b Labelle-Dumais C, Paré JF, Bélanger L, Farookhi R, Dufort D (August 2007). "Impaired progesterone production in Nr5a2+/- mice leads to a reduction in female reproductive function". Biology of Reproduction. 77 (2): 217–225. doi:10.1095/biolreprod.106.059121. PMID 17409375.
  13. ^ Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (September 2002). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology. 16 (9): 2065–2076. doi:10.1210/me.2001-0194. PMID 12198243.
  14. ^ Lee YK, Moore DD (January 2002). "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. doi:10.1074/jbc.M105161200. PMID 11668176.

Further reading

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