Affinage

Showing NR5A2 — LRH-1 is a alias.

NR5A2

Nuclear receptor subfamily 5 group A member 2 · UniProt O00482

Length
541 aa
Mass
61.3 kDa
Annotated
2026-06-10
100 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR5A2 (LRH-1; FTZ-F1 family) is a monomeric orphan nuclear receptor that functions as a sequence-specific, pioneer transcription factor governing developmental gene programs from the earliest embryo through organogenesis (PMID:36423263, PMID:38409506, PMID:25063451). Its DNA-binding region combines a zinc finger with a conserved C-terminal FTZ-F1/CTE box that confers monomeric recognition of the extended PyCAAGG-type motif and binds DNA without an obligate ligand (PMID:1448096, PMID:8668203, PMID:8164672). Structural work established that the FTZ-F1 box folds into a helix packing against the DBD to enable long-range communication with the ligand-binding domain and full transcriptional and coactivator output (PMID:16289203), while cryo-EM of an NR5A2-nucleosome complex showed the CTE loop competes with the nucleosomal DNA minor-groove anchor to release entry-exit DNA, defining the structural basis of NR5A2 pioneer activity (PMID:38409506). In the early embryo NR5A2 binds its motif within SINE B1/Alu elements at cis-regulatory regions, opens chromatin, and acts as a master regulator of zygotic genome activation and the first lineage segregation, directly controlling pluripotency genes (Nanog, Pou5f1/Oct4) and lineage factors (Gata6, Tead4, Gata3), with loss causing morula-stage arrest, mitotic failure, and segregation defects (PMID:36423263, PMID:37935903, PMID:39361745, PMID:38243114); consistent with this it can replace Oct4 in somatic reprogramming and, with Esrrb, sustains naive ESC self-renewal by controlling Oct4/Sox2/Nanog binding (PMID:20096661, PMID:34397088). In organogenesis NR5A2 drives pancreatic progenitor expansion and acinar differentiation through mutually reinforcing regulation with PTF1A and a network including MYC, GATA4, FOXA2, RBPJL and MIST1, and its loss destabilizes the acinar state and accelerates Kras-driven metaplasia and inflammation (PMID:25063451, PMID:23645620, PMID:29443959). In the ovary NR5A2 controls steroidogenesis and luteal progesterone synthesis via cholesterol-transport genes (Scarb1, Ldlr, Star) and granulosa cell proliferation (PMID:24552399, PMID:17409375, PMID:29379893). NR5A2 transcriptional output is modulated by LXXLL/homeodomain cofactors (Ftz, Prox1), p160/SRC and NCOA3 coactivators, SUMOylation, and phospholipid (PIP3) binding within its LBD, and is antagonized by the inflammatory transcription factors c-Jun/AP-1 and NF-κB (PMID:11592991, PMID:15143342, PMID:17015464, PMID:20096661, PMID:26416531, PMID:24570488, PMID:29443959).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1992 High

    Defined how the receptor achieves sequence-specific DNA recognition, establishing that an FTZ-F1 family receptor reads its element as a monomer using a dedicated basic box plus zinc finger.

    Evidence Gel mobility shift competition with mutant peptides for Drosophila FTZ-F1

    PMID:1448096

    Open questions at the time
    • Did not address mammalian ortholog function in vivo
    • No structural model of the FTZ-F1 box
  2. 1996 High

    Extended the family to mammals and showed the vertebrate receptor binds its element as a monomer without an obligate ligand and activates target promoters, with a C-terminal truncation acting dominant-negative.

    Evidence cDNA cloning, Kd measurement, and reporter assays with truncation mutants for rat FTF

    PMID:8668203

    Open questions at the time
    • Endogenous ligand undefined
    • Physiological target genes beyond AFP not yet mapped
  3. 1998 High

    Established the human gene (NR5A2/hB1F) as an FTZ-F1-family orphan receptor with defined DNA binding, transactivation, chromosomal locus, and splice isoforms.

    Evidence Yeast one-hybrid, binding and transactivation reporter assays, RT-PCR, FISH

    PMID:9786908

    Open questions at the time
    • Endogenous human target genes not yet defined
    • No in vivo function established
  4. 2001 High

    Resolved the cofactor logic of the receptor, showing homeodomain partners engage both the DBD and the AF-2 surface via LXXLL-like motifs, and that mammalian SF-1 can substitute functionally in flies.

    Evidence In vitro pulldowns, domain mapping, and in vivo genetic rescue in Drosophila

    PMID:11520662 PMID:11592991

    Open questions at the time
    • Did not identify vertebrate equivalents of these cofactors at the time
    • Structural basis of AF-2 docking not resolved
  5. 2005 High

    Provided the structural basis for DBD-LBD functional communication, showing the FTZ-F1 box helix is required for transcriptional activity and coactivator enhancement even though it does not contact DNA.

    Evidence X-ray crystallography of the human LRH-1 DBD-DNA complex with mutagenesis and reporter/coactivator assays

    PMID:16289203

    Open questions at the time
    • Did not address nucleosomal DNA engagement
    • Mechanism of long-range communication not fully defined
  6. 2006 High

    Established the in vivo requirement for NR5A2 in mammalian development, showing it acts in extraembryonic tissues for epiblast gastrulation.

    Evidence Knockout mice with tetraploid complementation and marker analysis

    PMID:17075876

    Open questions at the time
    • Did not resolve preimplantation roles
    • Direct target genes at gastrulation not mapped
  7. 2007 High

    Linked NR5A2 dosage causally to luteal steroidogenesis, showing reduced progesterone underlies the fertility defect and is rescued by progesterone supplementation.

    Evidence Nr5a2 heterozygous mice with hormone measurement and pharmacological rescue

    PMID:17409375

    Open questions at the time
    • Direct steroidogenic target genes not yet identified
    • Cell-autonomous requirement not separated from systemic effects
  8. 2010 High

    Connected NR5A2 to the pluripotency network, showing it can replace Oct4 in reprogramming, shares targets with Sox2/Klf4, activates Nanog, and is negatively regulated by SUMOylation.

    Evidence Reprogramming assays, sumoylation-site mutagenesis, and genome-wide ChIP-chip in mouse cells

    PMID:20096661

    Open questions at the time
    • Did not establish requirement in normal embryo pluripotency at this stage
    • SUMO-target sites mapped only functionally
  9. 2013 High

    Defined NR5A2 as a guardian of pancreatic acinar identity whose loss promotes metaplasia, inflammation, and Kras-driven neoplasia, linking it to NF-κB/STAT3 signaling.

    Evidence Conditional and heterozygous knockout mice with pancreatitis and Kras models, pathway analysis (two concurrent studies)

    PMID:23598351 PMID:23645620

    Open questions at the time
    • Direct target genes mediating acinar maintenance not yet mapped
    • Mechanism connecting NR5A2 loss to NF-κB/STAT3 hyperactivation unresolved
  10. 2014 High

    Established NR5A2 as a direct controller of pancreatic organogenesis through a mutually reinforcing regulatory network with PTF1A and other lineage factors.

    Evidence Conditional inactivation with genome-wide ChIP and co-binding analysis at shared regulatory regions

    PMID:25063451

    Open questions at the time
    • Did not resolve pioneer versus settler binding mode in this context
    • Hierarchy of NR5A2 versus PTF1A initiation not fully ordered
  11. 2014 High

    Defined direct ovarian steroidogenic and ovulatory targets, linking NR5A2 to Pgr and cholesterol-transport genes (Scarb1, Ldlr, Star) required for progesterone synthesis and ovulation.

    Evidence Granulosa-specific conditional knockout with hormone and gene expression analysis

    PMID:24552399

    Open questions at the time
    • Direct versus indirect regulation of Pgr not fully separated
    • Cofactor dependence in granulosa cells not addressed here
  12. 2014 High

    Showed inflammatory signaling antagonizes NR5A2 directly, with c-Jun and NF-κB physically interacting with NR5A2 to repress its steroidogenic target Cyp11a1.

    Evidence Reporter assays, protein interaction, dominant-negative experiments, and a mouse colitis model

    PMID:24570488

    Open questions at the time
    • Structural basis of NR5A2 repression by c-Jun/NF-κB unknown
    • Generality across NR5A2 target loci not established
  13. 2015 High

    Identified a phospholipid ligand mode, showing PIP3 binds the NR5A2 LBD with its tails buried and head group surface-exposed, stabilizing the domain.

    Evidence X-ray crystallography of the LBD-PIP3 complex with affinity and thermal stability measurement

    PMID:26416531

    Open questions at the time
    • Physiological relevance of PIP3 occupancy in vivo not demonstrated
    • Effect on coactivator recruitment not directly tested
  14. 2016 High

    Broadened the developmental remit of NR5A2 to neural stem cell fate, where it directs neurogenesis over astrogliogenesis through Ink4/Arf, Prox1, Notch1 and JAK/STAT.

    Evidence Gain- and loss-of-function in primary NSCs and mouse embryos with target/pathway analysis

    PMID:27447294

    Open questions at the time
    • Direct versus indirect regulation of listed targets not fully separated
    • Upstream control of NR5A2 in neural lineages partly inferred
  15. 2017 High

    Extended NR5A2 function to immune regulation, showing it directly drives FASLG transcription to control T cell apoptosis and cytotoxicity.

    Evidence ChIP, promoter mutagenesis, pharmacological inhibition, and a mouse hepatitis model

    PMID:28406481

    Open questions at the time
    • Cofactor requirements at FASLG not defined
    • Endogenous ligand controlling this activity unknown
  16. 2018 High

    Revealed a regulatory switch in which reduced NR5A2 relocates from differentiation to inflammatory gene promoters in an AP-1-dependent manner, mechanistically uniting differentiation and inflammation control.

    Evidence Transcriptomics, NR5A2 ChIP-seq, and conditional Jun knockout rescue in pancreas

    PMID:29443959

    Open questions at the time
    • Molecular trigger for promoter relocation unresolved
    • Whether relocation reflects altered cofactor availability not defined
  17. 2019 High

    Established a cell-intrinsic requirement for NR5A2 in T cell maturation, proliferation, and antiviral CD8+ responses.

    Evidence T cell-specific conditional knockout with proliferation, immunization, and viral challenge assays

    PMID:31328159

    Open questions at the time
    • Direct transcriptional targets in T cells not mapped here
    • Relationship to FASLG regulation not integrated
  18. 2022 High

    Defined a multi-step islet survival pathway, showing NR5A2 induces PTGS2/COX2 to raise PGE2 acting through PTGER1 to protect beta cells and drive proliferation.

    Evidence Beta cell-specific knockout with agonist treatment and pharmacological dissection of PTGS2/PTGER1

    PMID:35602948

    Open questions at the time
    • Direct NR5A2 occupancy at Ptgs2 not shown
    • Translation of agonist effects to human islets not established
  19. 2022 High

    Identified NR5A2 as an essential pioneer factor for zygotic genome activation, binding its motif in SINE B1/Alu elements to open chromatin and bind nucleosomal DNA.

    Evidence Embryo knockout, ATAC-seq, ChIP/CUT&RUN, in vitro nucleosome binding, and chemical inhibition

    PMID:36423263

    Open questions at the time
    • Exact arrest stage and extent of ZGA dependence later contested
    • Structural basis of nucleosome engagement not yet defined here
  20. 2024 High

    Reconciled embryonic phenotypes and clarified NR5A2 as primarily an 8-cell/morula-stage master regulator of lineage factors, mitosis, telomere maintenance and DNA repair, with loss causing chromosome segregation defects.

    Evidence Multiple knockout models with single-embryo transcriptomics and mitotic immunofluorescence, plus ChIP-seq across stages defining bipotency activation of ICM and TE genes

    PMID:37935903 PMID:38243114 PMID:39361745

    Open questions at the time
    • Mechanism linking NR5A2 to mitotic/DNA-repair gene control unresolved
    • How NR5A2 transitions from ICM to TE regulation not fully defined
  21. 2024 High

    Provided the structural mechanism of NR5A2 pioneer activity, showing the CTE loop competes with a nucleosomal minor-groove DNA anchor to release entry-exit DNA, with D159 required for stable nucleosome engagement.

    Evidence Cryo-EM of the NR5A2-nucleosome complex with D159 mutagenesis and DNA unwrapping assays

    PMID:38409506

    Open questions at the time
    • Does not define how cofactors stabilize the unwrapped state in cells
    • Sequence determinants of nucleosomal site selection not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous physiological ligand that tunes NR5A2 activity across these contexts, and how a single pioneer receptor is directed to context-specific gene programs, remain unresolved.
  • No defined endogenous ligand beyond in vitro PIP3 binding
  • Determinants of context-specific target selection unknown
  • Mechanism coupling chromatin opening to downstream coactivator recruitment in vivo not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 5 GO:0008289 lipid binding 1 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-1430728 Metabolism 2
Partners
ESRRBFTZHNF1JUNNCOA3PROX1PTF1A

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 FTZ-F1 is a member of the nuclear hormone receptor superfamily that binds the zebra element of the fushi tarazu (ftz) gene and activates ftz transcription, particularly in stripes 1, 2, 3, and 6 of the Drosophila embryo. cDNA cloning by recognition site screening, immunological cross-reaction, peptide sequence analysis, DNA binding assays Science High 1709303
1992 FTZ-F1 contains a conserved 30-amino-acid basic region (the FTZ-F1 box) C-terminal to the zinc finger motif; gel mobility shift competition assays showed the FTZ-F1 box governs recognition of the first three bases of the binding sequence (5'-PyCAAGGPyCPu-3') while the zinc finger recognizes the remainder, and FTZ-F1 binds DNA as a monomer. Gel mobility shift competition with mutant peptides, gel mobility shift matrix competition assay Molecular and cellular biology High 1448096
1992 Mouse ELP (embryonal long terminal repeat-binding protein) is a homolog of Drosophila FTZ-F1, both sharing conserved DNA-binding and putative ligand-binding domains and recognizing the same non-repeat DNA sequence element, functioning in undifferentiated embryonal carcinoma cells. cDNA cloning, sequence analysis, DNA binding assays Molecular and cellular biology Medium 1545809
1993 A developmental isoform of FTZ-F1 (beta FTZ-F1) is expressed from a mid-prepupal chromosome puff (75CD) in Drosophila and binds over 150 chromosomal targets including late prepupal puffs, implicating it as a regulator of insect metamorphosis downstream of ecdysone. cDNA cloning, indirect immunofluorescent staining on polytene chromosomes Proceedings of the National Academy of Sciences of the United States of America Medium 8096644
1994 FTZ-F1 alpha and FTZ-F1 beta both bind as monomers to the 9-bp F1RE in the ftz zebra element with similar affinities and sequence specificities, and both contribute to net transcriptional activity; they do not form heterodimers with each other. In vitro DNase I footprinting, gel mobility shift with recombinant proteins and N-terminally truncated receptors, cotransfection reporter assays Molecular and cellular biology High 8164672
1996 Rat FTF (fetoprotein transcription factor, ortholog of NR5A2) is an orphan nuclear receptor of the FTZ-F1 family that recognizes the DNA sequence 5'-TCAAGGTCA-3' and activates the alpha1-fetoprotein (AFP) promoter; it binds DNA as a monomer without requiring a specific ligand, and C-terminus-truncated FTF exerts dominant negative effects. cDNA cloning, DNA binding assays, transient transfection with deletion/truncation mutants, Kd measurements Molecular and cellular biology High 8668203
1996 The mammalian ftz-f1 gene (encoding Ad4BP/SF-1) contains an intronic Ad4 site to which Ad4BP itself binds, creating an autoregulatory loop that maintains high expression specifically in steroidogenic tissues; DNase I hypersensitivity showed this chromatin region is 'open' in adrenal and Y-1 cells but 'closed' in liver. Gel mobility shift assay, DNase I footprinting, DNase I hypersensitivity, site-directed mutagenesis, transient transfection The Journal of biological chemistry High 8626518
1996 FTZ-F1 directly regulates the pupal cuticle gene EDG84A in Drosophila: heat-induction of FTZ-F1 causes premature EDG84A expression; mutation of the FTZ-F1 binding site in the EDG84A promoter abolishes reporter expression in transgenic flies. Heat-shock induction of FTZ-F1 transgene, lacZ reporter transgenics, base substitution mutagenesis of FTZ-F1 binding site Molecular and cellular biology High 8887679
1997 Ftz-F1 (nuclear hormone receptor) and the homeodomain protein Ftz are present in a complex in Drosophila embryos; Ftz-F1 facilitates binding of Ftz to DNA and allows Ftz to interact with weak-affinity sites; embryos lacking Ftz-F1 display ftz-like pair-rule defects and fail to activate Ftz target genes despite Ftz being expressed. Co-immunoprecipitation from Drosophila embryo extracts, in vitro DNA binding facilitation assays, genetic analysis of ftz-f1 mutants Nature High 9020363 9020364
1997 Ftz and Ftz-F1 interact directly and specifically in vitro and in vivo through a conserved domain in Ftz; Ftz-F1 is an obligatory maternal cofactor for Ftz function in Drosophila segmentation. In vitro binding assays, in vivo genetic rescue experiments, domain mapping Nature High 9020363 9020364
1997 Ftz-F1 and Ftz cooperate to activate the engrailed gene via adjacent conserved binding sites in an engrailed enhancer; Ftz-F1 and Ftz bind these sites with 4- to 8-fold cooperativity, suggesting direct protein-protein contact. DNase I footprinting, gel mobility shift assay, transgenic reporter analysis, genetic epistasis Development High 9043065
1998 Human NR5A2 (hB1F) is an orphan nuclear receptor of the FTZ-F1 family that specifically binds the B1 region of hepatitis B virus enhancer II (ENII) and trans-activates ENII; mapped to chromosome 1q31-32.1; a splice isoform hB1F-2 with an extra 46 amino acids in the A/B region was identified. Yeast one-hybrid screening, DNA binding assays, transactivation reporter assays, RT-PCR, FISH The Journal of biological chemistry High 9786908
1999 Beta FTZ-F1 (Drosophila ortholog of NR5A2) functions as a competence factor for stage-specific responses to ecdysone during metamorphosis; beta FTZ-F1 mutants cannot respond properly to the prepupal ecdysone pulse and the ecdysone-triggered genetic hierarchy is severely attenuated, though ecdysone receptor expression is unaffected. Genetic analysis of beta FTZ-F1 loss-of-function mutants, molecular analysis of downstream ecdysone target gene expression Molecular cell High 10078197
2001 The Ftz-F1/Ftz interaction involves two surfaces: the Ftz-F1 DNA-binding domain interacts strongly with Ftz and facilitates Ftz binding to target DNA; the AF-2 domain of Ftz-F1 interacts with an LRALL sequence in Ftz (resembling nuclear receptor coactivator LXXLL motifs); murine SF-1 functionally substitutes for Drosophila Ftz-F1 in vivo, demonstrating evolutionary conservation. In vitro pulldown/binding assays, domain mapping with truncation mutants, in vivo genetic rescue experiments in Drosophila Mechanisms of development High 11520662
2001 Ftz acts as an LXXLL motif-dependent coactivator for the orphan receptor FTZ-F1: the Ftz LXXLL motif and FTZ-F1 AF-2 core/LBD are required for interaction as shown by mammalian two-hybrid assays; this interaction is required for FTZ-F1 activation of target genes in Drosophila embryos and for the cuticle phenotype. Mammalian one- and two-hybrid assays, LXXLL motif mutagenesis, transgenic fly analysis of target gene expression and cuticle phenotype Proceedings of the National Academy of Sciences of the United States of America High 11592991
2003 Human LRH-1/hB1F (NR5A2) and HNF1 directly interact in vitro and synergize to activate hepatitis B virus enhancer II (ENII) and initiate viral gene transcription and DNA replication even in non-hepatic cells; specific activation domains in both proteins contribute to this synergism. In vitro protein interaction assays, cotransfection reporter assays in non-hepatic cells, domain mapping Cell research Medium 14728801
2004 The homeodomain protein Prox1 functions as a co-repressor for human LRH-1 (NR5A2), demonstrating functional conservation of Drosophila Ftz/Ftz-F1 homeodomain–nuclear receptor interaction in vertebrates; Prox1 represses LRH-1 transcriptional activity in the enterohepatic system. Protein interaction assays, cotransfection reporter assays, characterization in liver cell lines EMBO reports Medium 15143342
2005 Crystal structure of the human LRH-1 (NR5A2) DBD-DNA complex at 2.2 Å shows the Ftz-F1 box folds into a novel helix that packs against the DBD but does not directly contact DNA; mutations disrupting Ftz-F1 helix positioning do not eliminate DNA binding but significantly reduce transcriptional activity and eliminate GRIP1 coactivator enhancement, revealing long-range DBD→LBD functional communication. X-ray crystallography, site-directed mutagenesis, transcriptional reporter assays, coactivator recruitment assays Journal of molecular biology High 16289203
2006 Beta FTZ-F1 potentiates ecdysone receptor (EcR) activity by recruiting a p160/SRC coactivator (FISC) through direct protein-protein interaction; this interaction dramatically increases FISC recruitment to the functional ecdysone receptor in a 20E-dependent manner, enhances local histone H4 acetylation, and drives stage-specific 20E effector gene expression during mosquito reproduction. Protein-protein interaction assays, ChIP, histone acetylation analysis, gene expression analysis in vivo Molecular and cellular biology High 17015464
2006 NR5A2 knockout mice display embryonic lethality around gastrulation: NR5A2-/- embryos show primitive streak formation failure and inability to generate embryonic or extraembryonic mesoderm; tetraploid complementation showed NR5A2 is required in extraembryonic tissues for epiblast gastrulation. Targeted gene disruption (knockout mice), morphological analysis, marker gene expression, tetraploid complementation aggregation experiments Developmental dynamics High 17075876
2007 Nr5a2 heterozygous female mice show reduced fertility arising from decreased circulating progesterone and impaired luteal function, without defects in follicular development, ovulation, or estrogen production; exogenous progesterone supplementation rescues reproductive ability, establishing Nr5a2 as an in vivo regulator of luteal steroidogenesis. Nr5a2+/- mice, hormone measurements, progesterone rescue experiment, reproductive outcome assessment Biology of reproduction High 17409375
2010 Nr5a2 (LRH-1) can replace Oct4 in the reprogramming of mouse somatic cells to iPSCs; sumoylation mutants of Nr5a2 with enhanced transcriptional activity further increase reprogramming efficiency; genome-wide location analysis shows Nr5a2 shares common gene targets with Sox2 and Klf4; Nr5a2 activates Nanog as part of its reprogramming mechanism. Retroviral reprogramming assay, sumoylation site mutagenesis, genome-wide ChIP-chip location analysis, Nanog reporter and expression analysis Cell stem cell High 20096661
2011 Small molecule agonists of LRH-1/NR5A2 can bind its ligand-binding domain; crystal structure of LRH-1 LBD bound to a synthetic agonist defined the binding pocket and guided structure-activity relationship studies yielding LRH-1-selective (RJW101) and dual LRH-1/SF-1 agonists (RJW100) with activity at endogenous target genes in human cell lines. X-ray crystallography of LBD-ligand complex, peptide recruitment assay, structure-activity relationship medicinal chemistry, endogenous gene expression assays Journal of medicinal chemistry High 21391689
2012 Drosophila FTZ-F1 interacts with juvenile hormone receptor candidates MET and GCE in a JH-dependent manner via AF-2/LXXLL (LIXXL) interaction; removal of FTZ-F1 helix 12 (AF2) severely reduces interaction; the interaction relies on hydrophobic contacts including a unique interaction with helix 4, without requiring canonical charge clamp residues. Insect two-hybrid assays, homology modeling, docking simulations, domain deletion analysis The Journal of biological chemistry Medium 22249180
2013 Nr5a2 conditional deletion in the pancreas leads to destabilization of mature acinar differentiation, acinar-to-ductal metaplasia, loss of regenerative capacity after pancreatitis, and dramatically accelerates Kras-driven acinar-to-ductal metaplasia and PDA precursor development. Conditional knockout mice (PdxCre-late; Nr5a2 c/c), caerulein pancreatitis model, histology, marker analysis Gut High 23645620
2013 Nr5a2 haploinsufficiency sensitizes the pancreas to caerulein-induced damage with increased acino-ductal metaplasia, impaired recovery, myeloid cell infiltration, and proinflammatory cytokine expression with hyperactivation of NF-κB and STAT3; a single acute pancreatitis episode cooperates with Kras(G12V) to accelerate preneoplastic lesion development. Nr5a2+/- and conditional Nr5a2 epithelial-specific knockout mice, caerulein pancreatitis model, molecular pathway analysis (NF-κB, STAT3) Gut High 23598351
2013 Drosophila Ftz-f1 is SUMOylated in vitro and in vivo; SUMO levels regulate Ftz-f1 expression, and Ftz-f1 in turn drives expression of scavenger receptor Snmp1, which mediates lipid uptake in steroidogenic tissues for ecdysteroid biosynthesis. In vitro and in vivo SUMOylation assays, RNAi knockdown in Drosophila, lipid staining, hormone titer measurements, genetic epistasis PLoS genetics Medium 23637637
2014 LRH-1 (NR5A2) initiates an ER stress resolution pathway independent of canonical UPR: in response to ER stress, LRH-1 induces expression of kinase Plk3, which phosphorylates and activates transcription factor ATF2; hepatic Lrh-1-null mice cannot resolve ER stress, and restoring Plk3 rescues ER stress resolution in Lrh-1-null cells; LRH-1 agonist treatment increases ER stress resistance. Hepatic conditional Lrh-1 knockout mice, Plk3 knockout mice, viral rescue of Plk3, ATF2 manipulation, ER stress induction assays, LRH-1 agonist treatment eLife High 24737860
2014 Nr5a2 granulosa-specific depletion prevents ovulation (at least partly through downregulation of the progesterone receptor gene Pgr) and impairs luteal function with reduced progesterone synthesis due to defects in cholesterol transport (down-regulation of Scarb1, Ldlr, Star). Conditional knockout mice (Nr5a2-Cyp19-Cre), hormone measurements, gene expression analysis, pseudopregnancy test Endocrinology High 24552399
2014 NR5A2 is required during pancreatic organogenesis for expansion of nascent pancreatic epithelium, formation of multipotent progenitor cells, and acinar differentiation; NR5A2 directly controls expression and regulatory interactions with PTF1A, MYC, GATA4, FOXA2, RBPJL, and MIST1; Nr5a2 and Ptf1a establish mutually reinforcing regulatory interactions and bind shared regulatory regions of pancreatic genes. Conditional gene inactivation, genome-wide binding analysis (ChIP), expression analysis, co-binding analysis at shared regulatory regions Development High 25063451
2014 TNF suppresses intestinal glucocorticoid synthesis by activating c-Jun and NF-κB, both of which physically interact with NR5A2 and repress Cyp11a1 reporter activity; dominant-negative JNK1 or IκB relieves repression; NR5A2 activity is thus antagonized by inflammatory signals to sustain chronic colitis. Reporter assays, protein interaction (c-Jun/NF-κB with NR5A2), dominant-negative experiments, mouse colitis model with TNF inhibitor rescue Science signaling High 24570488
2015 Crystal structure of human LRH-1 (NR5A2) LBD bound by PIP3 (PI(3,4,5)P3) at high affinity; the hydrophobic PIP3 tails are buried inside the LBD ligand-binding pocket while the negatively charged PIP3 head group is presented on the receptor surface, similar to PIP3-SF-1 binding mode; PIP3 binding stabilizes the LRH-1 LBD. X-ray crystallography of LBD-PIP3 complex, binding affinity measurement, thermal stability assay Journal of structural biology High 26416531
2016 NR5A2 controls neural stem cell fate decisions: overexpression promotes neurogenesis and inhibits astrogliogenesis; loss-of-function delays neuronal differentiation; NR5A2 directly regulates the Ink4/Arf locus, Prox1, Notch1 and JAK/STAT signaling; upstream regulation of NR5A2 involves proneural genes, Notch1, and JAK/STAT pathways. Overexpression and shRNA knockdown in primary neural stem cells and mouse embryos in utero, target gene expression analysis, pathway analysis Nature communications High 27447294
2016 In zebrafish, nr5a2 (ortholog of mammalian NR5A2) is required for acinar cell differentiation of the exocrine pancreas and for hepatic progenitor outgrowth and differentiation; chemical inhibition of Nr5a2 during hepatopancreas progenitor specification disrupts exocrine pancreas formation and enhances liver size, indicating Nr5a2 regulates hepatic vs. pancreatic progenitor fate choice. Targeted genetic null mutant in zebrafish, chemical antagonist (Cpd3) temporal inhibition, marker gene analysis Developmental biology High 27474396
2017 Nr5a2 is essential for granulosa cell proliferation: conditional knockout reduces proliferation (assessed by BrdU, PCNA, FACS); downregulates cyclin transcripts (Ccnd1, Ccnd2, Ccne1, Ccne2, E2f1, E2f2); pharmacological inhibition by ML180 reverse agonist or β-catenin inhibition similarly decreases cyclin transcripts, identifying β-catenin as an Nr5a2 cofactor in this process. Conditional knockout (Nr5a2-Amhr2-Cre), BrdU incorporation, PCNA immunostaining, FACS, microarray, ML180 pharmacological inhibition, β-catenin inhibitor treatment Journal of the Endocrine Society High 29379893
2017 LRH-1 (NR5A2) directly binds to LRH-1 binding sites in the FASLG (CD95L/FasL) promoter and drives FASLG promoter activity in T cells; mutation of LRH-1 binding sites reduces FASLG promoter activity; pharmacological inhibition of LRH-1 decreases activation-induced FasL expression and FasL-mediated T cell apoptosis and cytotoxicity. Chromatin immunoprecipitation, promoter reporter assays with binding site mutagenesis, pharmacological inhibition, T cell functional assays, mouse hepatitis model Cell death & disease High 28406481
2018 NR5A2 undergoes transcriptional relocation in Nr5a2+/- pancreatic tissue from differentiation-specific to inflammatory gene promoters; this promotes AP-1-dependent inflammatory gene transcription; pancreatic deletion of Jun rescues the pre-inflammatory phenotype and NR5A2 binding to inflammatory gene promoters; NR5A2 thus links differentiation and inflammatory programs. Global transcriptomic analysis, ChIP in pancreatic tissue, conditional Jun knockout rescue, NR5A2 ChIP-seq Nature High 29443959
2019 LRH-1/NR5A2 is required for T cell maturation and function: T cell-specific deletion causes drastic loss of mature peripheral T cells, strongly reduced activation-induced proliferation in vitro and in vivo, and failure to control viral infections by CD8+ T cells; LRH-1 is induced in T lymphocytes upon stimulation. T cell-specific LRH-1 conditional knockout mice, T cell proliferation assays, antigen immunization, viral infection challenge Science advances High 31328159
2020 NR5A2 synergizes with coactivator NCOA3 to upregulate NRF2 expression, thereby preventing BET inhibitor (BETi)-induced ferroptosis in breast cancer cells; inhibition of NR5A2 or NCOA3 enhances BETi anti-cancer effects in vitro and in vivo. siRNA knockdown, overexpression, small molecule inhibitors, Western blot, in vivo xenograft model Biochemical and biophysical research communications Medium 32536370
2020 LRH-1/NR5A2 inhibition reduces LPS-induced pro-inflammatory cytokine production in macrophages by downregulating LRH-1 targets glucokinase and glutaminase-2, thereby impairing mitochondrial ATP production and LPS-induced macrophage activation; in vivo LRH-1 inhibition reduces TNF production and liver damage in macrophage-dependent hepatitis. LRH-1 pharmacological inhibition, siRNA knockdown, metabolic assays (mitochondrial ATP), cytokine measurement, mouse hepatitis model Cell death & disease Medium 32111818
2021 Nr5a2 depletion from granulosa cells of primordial follicles impairs activation of primordial follicles into the growing pool: cKO ovaries have more primordial and fewer primary follicles; Nr5a2 loss induces changes in quiescence markers, follicle activation inhibitors, and regulators of migration/EMT. Conditional knockout from primordial follicles, follicle enumeration, in vitro culture, RNA sequencing Scientific reports Medium 33441767
2021 The combined activity of Esrrb and Nr5a2 is essential for naïve mouse ESC self-renewal: double depletion causes pluripotency network collapse and differentiation; Esrrb and Nr5a2 co-occupy a large common set of regulatory elements and control binding of Oct4, Sox2, and Nanog to DNA. Conditional double knockout in ESCs, ChIP-seq, transcriptome analysis Development High 34397088
2022 NR5A2/LRH-1 regulates the PTGS2-PGE2-PTGER1 pathway in pancreatic islets: LRH-1 ablation in beta cells blocks beta cell proliferation and abolishes agonist (BL001) anti-diabetic action; LRH-1 activation induces PTGS2/COX2 expression, increasing PGE2 levels; PGE2 acts via PTGER1 receptor to confer islet survival against cytokine-induced apoptosis. Beta cell-specific conditional knockout, agonist (BL001) treatment, PTGS2 inhibition, PTGER1 antagonist, cytochrome c release, PARP cleavage assays iScience High 35602948
2022 Nr5a2 is an essential pioneer factor for zygotic genome activation (ZGA) in mouse two-cell embryos: Nr5a2 is required for progression beyond the two-cell stage; it binds its motif within SINE B1/Alu retrotransposable elements in cis-regulatory regions of ZGA genes; NR5A2 promotes chromatin accessibility during ZGA and binds nucleosomal DNA in vitro; chemical inhibition indicates 72% of ZGA genes are regulated by Nr5a2. De novo motif search, Nr5a2 knockout in mouse embryos, ATAC-seq (chromatin accessibility), ChIP/CUT&RUN in embryos, in vitro nucleosome binding assays, chemical inhibition Science High 36423263
2023 NR5A2 connects ZGA to the first lineage segregation: Nr5a2 knockdown/knockout causes arrest at morula stage with impaired 4-8C gene activation; NR5A2 binds cis-regulatory elements enriched for B1 elements in both 2C and 8C embryos; NR5A2 is not required for global opening of 2C binding sites but is essential for opening 8C-specific sites; NR5A2 directly regulates key pluripotency genes (Nanog, Pou5f1/Oct4), primitive endoderm genes (Gata6), and trophectoderm genes (Tead4, Gata3) at the 8C stage. Nr5a2 knockdown and knockout in mouse embryos, genome-wide ChIP/CUT&RUN, ATAC-seq, transcriptome analysis Cell research High 37935903
2024 Cryo-EM structure of human NR5A2 bound to a nucleosome reveals the conserved CTE (carboxy-terminal extension) loop of the NR5A2 DNA-binding domain competes with a DNA minor groove anchor of the nucleosome, releasing entry-exit site DNA; mutational analysis showed NR5A2 D159 of the CTE is dispensable for free DNA binding but required for stable nucleosome association and persistent DNA unwrapping, establishing the mechanism of NR5A2 pioneer activity. Cryo-electron microscopy of NR5A2-nucleosome complex, site-directed mutagenesis (D159), nucleosome binding assays, DNA unwrapping assays Nature structural & molecular biology High 38409506
2024 NR5A2 acts as a bipotency activator in totipotent (2-8 cell) mouse embryos: NR5A2 binds and activates both early ICM and trophectoderm lineage genes at the 8-cell stage; upon trophoblast commitment, NR5A2 transitions from ICM to TE gene regulation; NR5A2 binding at 8C-specific sites controls key pluripotency and TE regulatory genes. Conditional Tfap2c and Nr5a2 depletion in mouse embryos, ChIP-seq in embryos at multiple developmental stages, transcriptomic analysis Nature structural & molecular biology High 38243114
2024 Nr5a2-/- mouse embryos arrest at early morula stage (not two-cell stage): Nr5a2 plays a minor role in ZGA but is a master regulator at the 8-cell stage controlling expression of lineage-specifying transcription factors and genes involved in mitosis, telomere maintenance, and DNA repair; Nr5a2-deficient embryos show frequent mitotic failure and chromosome segregation defects. Nr5a2 conditional and constitutive knockout mouse models, single-embryo transcriptomics, immunofluorescence for mitotic markers Science High 39361745

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell stem cell 382 20096661
1995 Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice. Developmental dynamics : an official publication of the American Association of Anatomists 305 8563022
1991 FTZ-F1, a steroid hormone receptor-like protein implicated in the activation of fushi tarazu. Science (New York, N.Y.) 270 1709303
1996 The alpha1-fetoprotein locus is activated by a nuclear receptor of the Drosophila FTZ-F1 family. Molecular and cellular biology 216 8668203
1999 The Drosophila beta FTZ-F1 orphan nuclear receptor provides competence for stage-specific responses to the steroid hormone ecdysone. Molecular cell 195 10078197
1992 A novel DNA-binding motif abuts the zinc finger domain of insect nuclear hormone receptor FTZ-F1 and mouse embryonal long terminal repeat-binding protein. Molecular and cellular biology 177 1448096
1997 The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein Ftz. Nature 166 9020364
1997 The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors. Nature 161 9020363
2005 Zebrafish sex determination and differentiation: involvement of FTZ-F1 genes. Reproductive biology and endocrinology : RB&E 147 16281973
1993 Potential role for a FTZ-F1 steroid receptor superfamily member in the control of Drosophila metamorphosis. Proceedings of the National Academy of Sciences of the United States of America 145 8096644
1992 Embryonal long terminal repeat-binding protein is a murine homolog of FTZ-F1, a member of the steroid receptor superfamily. Molecular and cellular biology 140 1545809
2013 Nr5a2 maintains acinar cell differentiation and constrains oncogenic Kras-mediated pancreatic neoplastic initiation. Gut 123 23645620
2022 Zygotic genome activation by the totipotency pioneer factor Nr5a2. Science (New York, N.Y.) 120 36423263
2000 nhr-25, the Caenorhabditis elegans ortholog of ftz-f1, is required for epidermal and somatic gonad development. Developmental biology 115 10772806
2018 Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas. Nature 109 29443959
1995 An E box element is required for the expression of the ad4bp gene, a mammalian homologue of ftz-f1 gene, which is essential for adrenal and gonadal development. The Journal of biological chemistry 104 7706291
2000 Expression and regulation of transcripts encoding two members of the NR5A nuclear receptor subfamily of orphan nuclear receptors, steroidogenic factor-1 and NR5A2, in equine ovarian cells during the ovulatory process. Endocrinology 102 11108279
2016 Downregulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression. Cell death & disease 94 27809310
1998 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 92 9786908
2006 The competence factor beta Ftz-F1 potentiates ecdysone receptor activity via recruiting a p160/SRC coactivator. Molecular and cellular biology 90 17015464
1999 Medaka (Oryzias latipes) FTZ-F1 potentially regulates the transcription of P-450 aromatase in ovarian follicles: cDNA cloning and functional characterization. Molecular and cellular endocrinology 87 10375033
1995 Steroidogenic factor 1 is the essential transcript of the mouse Ftz-F1 gene. Molecular endocrinology (Baltimore, Md.) 85 7491115
2000 The conserved nuclear receptor Ftz-F1 is required for embryogenesis, moulting and reproduction in Caenorhabditis elegans. Genes to cells : devoted to molecular & cellular mechanisms 83 10971653
2013 Nr5a2 heterozygosity sensitises to, and cooperates with, inflammation in KRas(G12V)-driven pancreatic tumourigenesis. Gut 82 23598351
2014 The nuclear hormone receptor family member NR5A2 controls aspects of multipotent progenitor cell formation and acinar differentiation during pancreatic organogenesis. Development (Cambridge, England) 77 25063451
1997 Ftz-F1 is a cofactor in Ftz activation of the Drosophila engrailed gene. Development (Cambridge, England) 71 9043065
1996 Regulation of the EDG84A gene by FTZ-F1 during metamorphosis in Drosophila melanogaster. Molecular and cellular biology 70 8887679
2010 ftz-f1 and Hr39 opposing roles on EcR expression during Drosophila mushroom body neuron remodeling. Nature neuroscience 63 21131955
2011 Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2). Journal of medicinal chemistry 62 21391689
1994 FTZ-F1-related orphan receptors in Xenopus laevis: transcriptional regulators differentially expressed during early embryogenesis. Molecular and cellular biology 60 8139576
2015 Interplay among Drosophila transcription factors Ets21c, Fos and Ftz-F1 drives JNK-mediated tumor malignancy. Disease models & mechanisms 59 26398940
2014 Involvement of FTZ-F1 in the regulation of pupation in Leptinotarsa decemlineata (Say). Insect biochemistry and molecular biology 59 25446391
1994 The Drosophila nuclear receptors FTZ-F1 alpha and FTZ-F1 beta compete as monomers for binding to a site in the fushi tarazu gene. Molecular and cellular biology 59 8164672
2014 Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution. eLife 57 24737860
2014 The orphan nuclear receptor Nr5a2 is essential for luteinization in the female mouse ovary. Endocrinology 56 24552399
2004 Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ-F1 homologue. EMBO reports 55 15143342
1997 Temporal regulation of the mid-prepupal gene FTZ-F1: DHR3 early late gene product is one of the plural positive regulators. Genes to cells : devoted to molecular & cellular mechanisms 54 9413997
1990 Identification and purification of a Bombyx mori homologue of FTZ-F1. Nucleic acids research 54 2124348
2013 Scavenger receptors mediate the role of SUMO and Ftz-f1 in Drosophila steroidogenesis. PLoS genetics 53 23637637
1993 FTZ-F1 beta, a novel member of the Drosophila nuclear receptor family. Mechanisms of development 53 8382937
2005 Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity. Journal of molecular biology 52 16289203
1997 Molecular cloning of chicken FTZ-F1-related orphan receptors. Gene 52 9332374
2015 Structure of Liver Receptor Homolog-1 (NR5A2) with PIP3 hormone bound in the ligand binding pocket. Journal of structural biology 51 26416531
2023 NR5A2 connects zygotic genome activation to the first lineage segregation in totipotent embryos. Cell research 49 37935903
2001 The nuclear receptor Ftz-F1 and homeodomain protein Ftz interact through evolutionarily conserved protein domains. Mechanisms of development 48 11520662
2005 Gene duplication, gene loss and evolution of expression domains in the vertebrate nuclear receptor NR5A (Ftz-F1) family. The Biochemical journal 46 15725073
1997 Teleost FTZ-F1 homolog and its splicing variant determine the expression of the salmon gonadotropin IIbeta subunit gene. Molecular endocrinology (Baltimore, Md.) 45 9178748
2007 The mRNA expression of P450 aromatase, gonadotropin beta-subunits and FTZ-F1 in the orange-spotted grouper (Epinephelus Coioides) during 17alpha-methyltestosterone-induced precocious sex change. Molecular reproduction and development 44 17075797
2002 A functionally conserved member of the FTZ-F1 nuclear receptor family from Schistosoma mansoni. European journal of biochemistry 42 12423370
2012 The Drosophila juvenile hormone receptor candidates methoprene-tolerant (MET) and germ cell-expressed (GCE) utilize a conserved LIXXL motif to bind the FTZ-F1 nuclear receptor. The Journal of biological chemistry 39 22249180
2006 Nuclear receptor NR5A2 is required for proper primitive streak morphogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 39 17075876
2003 LRH-1/hB1F and HNF1 synergistically up-regulate hepatitis B virus gene transcription and DNA replication. Cell research 38 14728801
2011 FTZ-F1 and FOXL2 up-regulate catfish brain aromatase gene transcription by specific binding to the promoter motifs. Biochimica et biophysica acta 37 22019437
1998 Adrenocortical and gonadal expression of the mammalian Ftz-F1 gene encoding Ad4BP/SF-1 is independent of pituitary control. Journal of biochemistry 37 9644266
2017 The Orphan Nuclear Receptor Liver Homolog Receptor-1 (Nr5a2) Regulates Ovarian Granulosa Cell Proliferation. Journal of the Endocrine Society 36 29379893
2024 Lineage regulators TFAP2C and NR5A2 function as bipotency activators in totipotent embryos. Nature structural & molecular biology 35 38243114
2014 Function of the nuclear receptor FTZ-F1 during the pupal stage in Drosophila melanogaster. Development, growth & differentiation 35 24611773
1996 Autoregulatory loop in the regulation of the mammalian ftz-f1 gene. The Journal of biological chemistry 35 8626518
2019 Transcription factor FTZ-F1 and cis-acting elements mediate expression of CYP6BG1 conferring resistance to chlorantraniliprole in Plutella xylostella. Pest management science 34 30471186
2006 Transcriptional regulation of the rainbow trout CYP19a gene by FTZ-F1 homologue. The Journal of steroid biochemistry and molecular biology 34 16621513
2016 Nuclear receptor NR5A2 controls neural stem cell fate decisions during development. Nature communications 33 27447294
2016 Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development. Developmental biology 33 27474396
2014 Tumor necrosis factor suppresses NR5A2 activity and intestinal glucocorticoid synthesis to sustain chronic colitis. Science signaling 33 24570488
2020 Dissecting the roles of FTZ-F1 in larval molting and pupation, and the sublethal effects of methoxyfenozide on Helicoverpa armigera. Pest management science 32 33078511
2017 Effect of NR5A2 inhibition on pancreatic cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) markers. Molecular carcinogenesis 32 27996162
2007 Impaired progesterone production in Nr5a2+/- mice leads to a reduction in female reproductive function. Biology of reproduction 32 17409375
2021 The combined action of Esrrb and Nr5a2 is essential for murine naïve pluripotency. Development (Cambridge, England) 31 34397088
2019 Nr5a2 promotes cancer stem cell properties and tumorigenesis in nonsmall cell lung cancer by regulating Nanog. Cancer medicine 31 30740909
2001 Characterization of the genomic structure and tissue-specific promoter of the human nuclear receptor NR5A2 (hB1F) gene. Gene 31 11595170
2000 Zebrafish ftz-f1 gene has two promoters, is alternatively spliced, and is expressed in digestive organs. The Biochemical journal 30 10816440
2020 NR5A2 synergizes with NCOA3 to induce breast cancer resistance to BET inhibitor by upregulating NRF2 to attenuate ferroptosis. Biochemical and biophysical research communications 29 32536370
2018 Hormonal control and target genes of ftz-f1 expression in the honeybee Apis mellifera: a positive loop linking juvenile hormone, ftz-f1, and vitellogenin. Insect molecular biology 29 30270498
2000 Two isoforms of FTZ-F1 messenger RNA: molecular cloning and their expression in the frog testis. Gene 28 10806365
2020 Nuclear receptor Ftz-f1 promotes follicle maturation and ovulation partly via bHLH/PAS transcription factor Sim. eLife 27 32338596
2001 Developmental expression patterns of FTZ-F1 homologues in zebrafish (Danio rerio). General and comparative endocrinology 27 11178880
2021 A role for orphan nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) in primordial follicle activation. Scientific reports 26 33441767
2017 Juvenile hormone biosynthesis in adult Blattella germanica requires nuclear receptors Seven-up and FTZ-F1. Scientific reports 26 28074850
2020 Pharmacological LRH-1/Nr5a2 inhibition limits pro-inflammatory cytokine production in macrophages and associated experimental hepatitis. Cell death & disease 25 32111818
2001 Segmentation gene product Fushi tarazu is an LXXLL motif-dependent coactivator for orphan receptor FTZ-F1. Proceedings of the National Academy of Sciences of the United States of America 25 11592991
1995 A naturally occurring short variant of the FTZ-F1-related nuclear orphan receptor xFF1rA and interactions between domains of xFF1rA. Molecular endocrinology (Baltimore, Md.) 25 7476970
2019 The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions. Science advances 24 31328159
2024 Nucleosome-bound NR5A2 structure reveals pioneer factor mechanism by DNA minor groove anchor competition. Nature structural & molecular biology 22 38409506
2021 NR5A2 transcriptional activation by BRD4 promotes pancreatic cancer progression by upregulating GDF15. Cell death discovery 22 33850096
2021 Nuclear receptor subfamily 5 group A member 2 (NR5A2): role in health and diseases. Molecular biology reports 22 34643922
2018 Genome-Wide Screening and Functional Analysis Reveal That the Specific microRNA nlu-miR-173 Regulates Molting by Targeting Ftz-F1 in Nilaparvata lugens. Frontiers in physiology 22 30618850
2017 Liver receptor homolog-1 (NR5a2) regulates CD95/Fas ligand transcription and associated T-cell effector functions. Cell death & disease 21 28406481
2013 The evolving role of the orphan nuclear receptor ftz-f1, a pair-rule segmentation gene. Evolution & development 21 24261442
2022 NR5A2/LRH-1 regulates the PTGS2-PGE2-PTGER1 pathway contributing to pancreatic islet survival and function. iScience 20 35602948
2020 Nuclear-mitochondrial crosstalk: On the role of the nuclear receptor liver receptor homolog-1 (NR5A2) in the regulation of mitochondrial metabolism, cell survival, and cancer. IUBMB life 20 32931651
2019 Nr5a2 promotes tumor growth and metastasis of gastric cancer AGS cells by Wnt/beta-catenin signaling. OncoTargets and therapy 20 31114234
2013 NR5A2 regulates Lhb and Fshb transcription in gonadotrope-like cells in vitro, but is dispensable for gonadotropin synthesis and fertility in vivo. PloS one 20 23536856
2006 Identification and characterization of a novel fushi tarazu factor 1 (FTZ-F1) nuclear receptor in Schistosoma mansoni. Molecular and biochemical parasitology 20 16870276
2005 A FTZ-F1-containing yeast artificial chromosome recapitulates expression of steroidogenic factor 1 in vivo. Molecular endocrinology (Baltimore, Md.) 20 15961510
2020 Transcription factor FTZ-F1 regulates mosquito cuticular protein CPLCG5 conferring resistance to pyrethroids in Culex pipiens pallens. Parasites & vectors 19 33054862
2014 Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells. Biochemical and biophysical research communications 19 24632207
2024 Nr5a2 is dispensable for zygotic genome activation but essential for morula development. Science (New York, N.Y.) 18 39361745
2017 Ovary-specific depletion of the nuclear receptor Nr5a2 compromises expansion of the cumulus oophorus but not fertilization by intracytoplasmic sperm injection. Biology of reproduction 18 28520915
2014 Retinoic acid receptor γ (Rarg) and nuclear receptor subfamily 5, group A, member 2 (Nr5a2) promote conversion of fibroblasts to functional neurons. The Journal of biological chemistry 18 24459144
2006 Computational identification of Ftz/Ftz-F1 downstream target genes. Developmental biology 18 16996052
1998 Candidate genes in complete and partial XY sex reversal: mutation analysis of SRY, SRY-related genes and FTZ-F1. Molecular and cellular endocrinology 18 9722168

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