Affinage

POU1F1

Pituitary-specific positive transcription factor 1 · UniProt P28069

Length
291 aa
Mass
32.9 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POU1F1 (GHF-1/Pit-1) is a pituitary-specific POU-homeodomain transcription factor that specifies and expands the somatotrope, lactotrope, and thyrotrope lineages and directly drives their hormone gene programs (PMID:8096199). Its C-terminal homeodomain is sufficient for sequence-specific DNA binding while the POU-specific domain stimulates that binding without contacting DNA directly, and transcriptional activation is carried by a separate hydroxylated amino-acid-rich domain (PMID:2902927, PMID:2574416). The factor binds and activates cell-specific elements of the GH and PRL promoters — reconstituting their activation when introduced into non-pituitary cells (PMID:2563596, PMID:2284007) — and binds A-T-rich elements of the TSHβ gene to confer TRH responsiveness (PMID:1901656, PMID:8364038). At the human GH locus it occupies multiple sites in the locus control region HSII enhancer and is required for POU1F1-dependent histone acetylation/methylation and high-level hGH-N expression (PMID:10446901, PMID:22094313). POU1F1 also acts as a signal integrator: it forms a composite element with Ets-1 to confer Ras responsiveness (PMID:8798730), cooperates with nuclear hormone receptors (RXR/RAR/TR, VDR) through direct interaction and ternary-complex formation on target promoters (PMID:9737723, PMID:9765286, PMID:10406465), and recruits the coactivator CBP, an interaction disrupted by IGF-1 receptor signaling to inhibit GH expression (PMID:16968807, PMID:22890843). Its activity is gated by M-phase-specific phosphorylation at Thr-220 that transiently inhibits DNA binding (PMID:8524234), by Musashi1-mediated translational repression of its mRNA that is relieved by leptin signaling (PMID:33373440, PMID:27571135), and by alternative splicing that generates a repressive beta isoform (PMID:34270938, PMID:33886498). Loss-of-function and dominant-negative POU1F1 variants — affecting DNA binding, transactivation, cofactor interaction, or splicing — cause combined pituitary hormone deficiency (PMID:15928241, PMID:16968807, PMID:34270938, PMID:36427334, PMID:11297581). In cancer contexts POU1F1 transcriptionally activates LDHA to drive glycolytic reprogramming and CXCL12 to recruit and M2-polarize macrophages, promoting tumor growth and metastasis (PMID:31292963, PMID:33714987).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1989 High

    Establishing how DNA recognition and activation are partitioned within the protein defined POU1F1 as a modular POU-homeodomain factor.

    Evidence cDNA cloning, DNase I footprinting with recombinant protein, and domain deletion/truncation with in vitro transcription readouts

    PMID:2574416 PMID:2902927

    Open questions at the time
    • No structural model of the DNA-bound complex
    • Role of the POU-specific domain in stimulating binding defined functionally but not structurally
  2. 1990 High

    Demonstrating direct binding and reconstituted activation of GH and PRL promoters established POU1F1 as the cell-specific activator of these hormone genes.

    Evidence Protein purification, gel-shift, in vitro transcription, and cotransfection reconstitution in non-pituitary HeLa cells

    PMID:2284007 PMID:2563596

    Open questions at the time
    • Early purified protein did not bind PRL promoter, later resolved by reconstitution
    • Did not address chromatin context of native loci
  3. 1993 High

    Resolving whether POU1F1 is required for lineage formation versus only hormone transcription showed it is needed for somatotrope/lactotrope generation in vivo.

    Evidence Transgenic mouse with GHF-1 promoter driving SV40 T-antigen, derived progenitor cell lines, and enhancer assay

    PMID:8096199

    Open questions at the time
    • Did not define the upstream specification cascade
    • Mechanism of lineage expansion versus maintenance not separated
  4. 1993 Medium

    Mapping A-T-rich TSHβ elements extended POU1F1's direct target repertoire to thyrotrope hormone genes and TRH responsiveness.

    Evidence Gel-shift with antibody supershift, in vitro-translated protein binding, and transfection reporter assays on rat/human TSHβ

    PMID:1901656 PMID:8364038

    Open questions at the time
    • TRH signaling link to POU1F1 occupancy not mechanistically resolved
    • Relative contributions of the three elements in vivo unknown
  5. 1996 High

    Showing POU1F1 forms a composite Ets-1 element established it as a cell-specific integrator of Ras/Raf signaling.

    Evidence Promoter mutagenesis, luciferase reporter, EMSA, and transfer of the composite element to a heterologous promoter

    PMID:8798730

    Open questions at the time
    • Direct POU1F1-Ets-1 contact not biochemically mapped
    • Other Ras-responsive POU1F1 targets not catalogued
  6. 1998 Medium

    Demonstrating physical interaction with nuclear hormone receptors explained how POU1F1 converts receptor-mediated repression into ligand-dependent GH activation.

    Evidence GST pull-down, ternary-complex EMSA, and reporter assays with domain-deleted receptors in pituitary and HeLa cells

    PMID:9737723 PMID:9765286

    Open questions at the time
    • Interaction surfaces not mapped at residue level
    • In vivo relevance to physiological GH regulation not tested
  7. 1995 High

    Identifying M-phase Thr-220 phosphorylation revealed cell-cycle gating of POU1F1 DNA binding by a non-Cdc2/non-PKA mitotic kinase.

    Evidence In vivo and in vitro kinase assays, site-directed mutagenesis, cell synchronization, and DNA-binding readouts

    PMID:8524234

    Open questions at the time
    • Identity of the mitotic kinase unknown
    • Consequence for hormone gene output across the cycle not quantified
  8. 2012 High

    Tracing IGF-1 inhibition to disruption of the POU1F1/CBP complex provided a coactivator-level mechanism for negative feedback on GH.

    Evidence ChIP, luciferase reporter, and a CBP S436A phospho-dead knock-in mouse with serum GH measurement

    PMID:16968807 PMID:22890843

    Open questions at the time
    • Kinase phosphorylating CBP S436 downstream of IGF-1R not defined here
    • Whether other coactivators substitute is unknown
  9. 2008 Medium

    Identifying LHX4 and OTX2 as direct activators of the POU1F1 promoter placed POU1F1 within an upstream transcriptional hierarchy of pituitary development.

    Evidence Recombinant binding and transactivation reporter assays comparing wild-type versus CPHD-patient mutant LHX4/OTX2

    PMID:15998782 PMID:18628516

    Open questions at the time
    • Combinatorial regulation of the POU1F1 promoter not resolved
    • Some regulatory elements are human-specific, limiting cross-species inference
  10. 2021 Medium

    Showing Musashi1 translationally represses Pou1f1 mRNA, reversibly via leptin, revealed a post-transcriptional and metabolic control layer over POU1F1 abundance.

    Evidence RNA immunoprecipitation, translational reporter, leptin receptor conditional knockout, and somatotrope purification

    PMID:27571135 PMID:33373440

    Open questions at the time
    • Sex-dependence of leptin control mechanistically unexplained
    • Other RBPs acting on Pou1f1 mRNA not surveyed
  11. 2022 High

    Systematic splicing variant assays and knock-in models established that shifting the alpha/beta isoform balance toward a repressive beta isoform causes dominant-negative CPHD.

    Evidence High-throughput splicing reporter (1,070 SNVs), repressor activity assays, multi-family co-segregation, and CRISPR knock-in mice

    PMID:33886498 PMID:34270938 PMID:36427334

    Open questions at the time
    • Beta-isoform target genes and repression mechanism not fully defined
    • Tissue-specific splicing regulators controlling the alpha/beta ratio unknown
  12. 2021 Medium

    Defining POU1F1 targets in tumor cells (LDHA, CXCL12, Mre11) showed it drives metabolic reprogramming, immune microenvironment remodeling, and altered DNA repair outside the pituitary.

    Evidence shRNA/overexpression, ChIP, reporter assays, Co-IP with ERK/HMGA, and xenograft/zebrafish models with PET imaging and macrophage profiling

    PMID:25788520 PMID:31292963 PMID:33714987 PMID:33927188

    Open questions at the time
    • What activates POU1F1 in non-pituitary tumors only partially defined (HMGA1B/2, FGFR2/ERK)
    • Direct versus indirect status of some cancer targets not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse POU1F1 control layers — mitotic phosphorylation, coactivator switching, translational repression, and alpha/beta splicing — are coordinated in vivo to set lineage-specific hormone output remains unresolved.
  • No integrated model linking the regulatory inputs
  • Identity of the M-phase kinase and the beta-isoform repressive program still open
  • Structural basis of DNA and cofactor recognition not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 6
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3
Partners
CREBBPELK1ETS1LHX3PITX1RXRTRVDR

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 GHF-1 (POU1F1) is a homeobox-containing protein; the homeodomain region near its C-terminus functions as its DNA-binding domain, demonstrated by DNase I footprinting with bacterially expressed GHF-1 fusion protein. cDNA cloning, sequence analysis, DNase I footprinting with bacterially expressed fusion protein Cell High 2902927
1989 The GHF-1/POU1F1 homeodomain is sufficient for sequence-specific DNA binding; the POU-specific domain stimulates DNA binding but does not contact DNA directly; transcriptional activation is mediated by a separate hydroxylated amino-acid-rich domain. Domain deletion/truncation analysis, in vitro transcription, DNA-binding assays Nature High 2574416
1989 Purified GHF-1/POU1F1 (33 kDa) binds to and activates the GH promoter but does not recognize the prolactin (Prl) promoter; a distinct factor in the same extracts binds the Prl promoter. Protein purification, gel-shift assay, in vitro transcription, immunoblotting Science High 2563596
1988 Extinction of GH expression in fibroblast × pituitary cell hybrids occurs via repression of GHF-1/POU1F1 protein and mRNA, not via a direct repressor of the GH promoter. Somatic cell hybridization, in vivo transfection, in vitro transcription, DNase I footprinting, immunoblotting Cell High 3167985
1990 POU1F1/Pit-1 binds to and activates cell-specific elements in both the GH and PRL gene promoters; 31 and 33 kDa nuclear proteins recognized by a Pit-1/GHF-1 antibody bind these elements in pituitary cells; cotransfection of RSV-Pit-1/GHF-1 into non-pituitary HeLa cells reconstitutes activation of both promoters. Protein-DNA binding assays, cotransfection/reporter assay, immunoblotting with Pit-1 antibody Molecular endocrinology High 2284007
1990 Sp1 binding to its site on the human GH promoter is mutually exclusive with GHF-1 binding to its distal site (demonstrated by DNase I footprinting), and Sp1 can partially compensate for low GHF-1 concentrations in stimulating transcription. DNase I footprinting, cell-free transcription assay Molecular and cellular biology Medium 2181288
1991 POU1F1/Pit-1 (or a closely related protein) mediates TRH responsiveness of the human TSHβ (TSHB) gene via a binding site at -128 to -92 bp; demonstrated by DNase I footprinting with thyrotropic tumor extract and transfection studies with an N-terminal deletion of Pit-1/GHF-1. DNase I footprinting, deletion analysis, transient transfection with reporter gene Proceedings of the National Academy of Sciences of the United States of America Medium 1901656
1993 GHF-1/POU1F1 is required for generation of somatotropes and lactotropes and for GH and PRL gene expression during pituitary development; immortalization of GHF-1-expressing progenitors that lack GH/PRL results in dwarfism, and an early-acting GHF-1 transcriptional enhancer was identified in this progenitor context. Transgenic mouse model (GHF-1 promoter driving SV40 T-antigen), cell line derivation, functional enhancer assay Genes & development High 8096199
1993 POU1F1/Pit-1 binds to three A-T-rich regions (TSH A, B, C) in the 5'-flanking region of the rat TSHβ gene; TSH A and TSH C each confer TRH-stimulated and/or enhanced basal activity to a heterologous promoter, and all three elements bind in vitro-translated Pit-1 with defined affinities. Gel mobility shift assay with antibody supershift, transient transfection reporter assay, in vitro translated protein binding Biochemistry Medium 8364038
1995 GHF-1/POU1F1 undergoes M-phase-specific phosphorylation at Thr-220 (within the N-terminal arm of the homeodomain) by a novel mitotic kinase activity distinct from Cdc2 or PKA, transiently inhibiting its DNA-binding activity during mitosis; PKA does not phosphorylate this inhibitory site in living cells. In vivo phosphorylation analysis, in vitro kinase assays, site-directed mutagenesis, cell synchronization, DNA-binding assays Molecular and cellular biology High 8524234
1995 GHF-1/POU1F1 and PKA synergistically activate the rat PRL promoter via the FP I site; GHF-1 is necessary but not sufficient for the full PKA response, which also requires a GHF-1-independent ubiquitous factor acting at FP I. Cotransfection reconstitution assay in HeLa cells with expression vectors, site-specific mutagenesis, luciferase reporter Molecular endocrinology Medium 7659093
1995 GHRH increases GHF-1/POU1F1 mRNA levels via a transcriptional mechanism not requiring new protein synthesis; IGF-1 inhibits basal GHF-1 mRNA and blocks GHRH induction; somatostatin has no effect. Primary anterior pituitary cell culture, Northern blotting, actinomycin D and cycloheximide treatments, pharmacological activation of second messengers Endocrinology Medium 7649093
1995 Retinoic acid induces GHF-1/POU1F1 mRNA and protein expression in pituitary cell lines via sequences between -400 and -90 bp of the GHF-1/Pit-1 promoter containing two CREs, both of which are required; T3 decreases GHF-1 mRNA and promoter activity in GH4C1 cells and blocks RA stimulation. Northern blotting, Western blotting, gel retardation assay, promoter-reporter transfection with deletion constructs Endocrinology Medium 7588287
1995 T3 represses GHF-1/POU1F1 gene expression by transcriptional interference with CRE-containing promoter elements (bp -90 to -200), not through a canonical TRE, and also interferes with GHF-1 binding to a positive autoregulatory element at bp -45 to -63. Promoter-reporter transfection with deletion constructs, in vitro DNA-binding assay, RT-PCR/Northern Molecular and cellular biology Medium 7565785
1996 POU1F1/GHF-1 functions as a cell-specific integrator of Ras signaling by forming a composite binding site with Ets-1 at positions -217 to -190 of the rat PRL promoter; both Ets-1 and GHF-1 binding sites are required for Ras/Raf activation; the composite element confers Ras responsiveness when inserted into the GH promoter. Site-directed mutagenesis of promoter, luciferase reporter assay, EMSA, insertion of composite element into heterologous promoter The Journal of biological chemistry High 8798730
1998 GHF-1/POU1F1 physically interacts with RXR (strong), RAR (weak), and TR (weak) via in vitro GST pull-down; GHF-1 and TR/RXR or RAR/RXR heterodimers form a ternary complex with the GH promoter fragment, and GHF-1 increases receptor binding to the promoter under limiting conditions. GST pull-down (in vitro binding), EMSA (ternary complex), reporter assay FASEB journal Medium 9737723
1998 In pituitary cells, GHF-1/POU1F1 converts T3/RA receptor-mediated repression into ligand-dependent activation of the GH promoter; a truncated T3 receptor lacking N-terminus and DNA-binding domain still activates the GH promoter in the presence of GHF-1 and RXR, indicating protein-protein interaction is sufficient. Transient transfection reporter assay in HeLa cells with/without GHF-1, GH promoter activity measurement The Journal of biological chemistry Medium 9765286
1999 VDR and GHF-1/Pit-1 synergistically activate the PRL promoter; coactivators CBP and SRC-1 enhance VDR-mediated activation via the AF-2 domain; CBP also enhances GHF-1-mediated activation of the PRL promoter. Transient transfection reporter assay in HeLa cells, cotransfection with VDR, GHF-1, SRC-1, and CBP expression vectors, AF-2 mutant analysis Molecular endocrinology Medium 10406465
1999 POU1F1/Pit-1 directly binds the serum response element (SRE) in the c-fos promoter (albeit with lower affinity than its cognate site) and activates c-fos transcription in a phosphorylation-dependent manner; Pit-1 phosphorylation sites are required for c-fos promoter activity but not for hormonal gene regulation. Gel shift analysis, overexpression in PC12 cells, antisense-mediated knockdown in GH3 cells, reporter assay with mutant Pit-1 phosphorylation sites Molecular endocrinology Medium 10319324
1999 POU1F1/Pit-1 binds A/T-rich sequences within a 203-bp enhancer element of the human GH locus control region (LCR) HSII region and is required for enhancer activity in pituitary cells in culture and in transgenic mice. EMSA (competition and antibody supershift with recombinant protein), deletion analysis, promoter-reporter transfection, transgenic mouse reporter Molecular endocrinology High 10446901
2005 POU1F1 mutation E230K reduces transactivation but not DNA-binding affinity; R172Q reduces both DNA binding and transactivation; ins778A abolishes DNA binding and reduces transactivation — demonstrating mutation-specific functional defects in the context of CPHD. Functional studies: transactivation reporter assay, DNA-binding affinity assay (EMSA or similar) The Journal of clinical endocrinology and metabolism Medium 15928241
2005 LHX4 binds to a human-specific element in the POU1F1 upstream regulatory sequence and activates POU1F1 transcription; mutant LHX4 proteins from CPHD patients fail to bind and activate the POU1F1 regulatory sequence but do not act as dominant negatives over normal LHX4. Recombinant protein expression in CHO cells, DNA-binding assay, reporter/transactivation assay The Journal of clinical endocrinology and metabolism Medium 15998782
2008 OTX2 binds to target sequences within the POU1F1 promoter and markedly transactivates it (~19-fold); a frameshift OTX2 mutation retaining the homeodomain but losing the transactivation domain barely retains this activity with no dominant-negative effect. Transfection reporter (luciferase) assay, nuclear localization assay, OTX2 wild-type vs. mutant comparison The Journal of clinical endocrinology and metabolism Medium 18628516
2008 POU1F1 mutation S179R (in the POU-specific domain) abolishes interaction with coactivator CBP on the PRL promoter (but not with LHX3) and markedly reduces DNA binding and transactivation, with normal nuclear accumulation. Transactivation reporter assay, EMSA (DNA binding), nuclear accumulation assay, functional interaction studies in alphaT3 cells The Journal of clinical endocrinology and metabolism Medium 16968807
2008 POU1F1 proliferative response to GHRH is cell-type specific and requires Pit-1/GHF-1 expression; Pit-1 is needed for downstream GHRH receptor signaling effects on cell proliferation (p27 degradation), demonstrated by Pit-1 siRNA knockdown in GH3-GHRHR cells and by exogenous Pit-1 expression in CHO-4 cells. siRNA knockdown, overexpression, cell proliferation assays, Western blotting for cell cycle regulators Journal of cellular physiology Medium 17941086
2009 POU1F1 binds directly to a site near the Syt1 (synaptotagmin I) initiation exon in GH3 pituitary cells (ChIP, in vitro binding), and POU1F1 knockdown reduces endogenous Syt1 mRNA; luciferase reporter assays confirm a POU1F1-regulated internal Syt1 promoter. Chromatin immunoprecipitation (ChIP), shRNA knockdown, in vitro DNA binding, luciferase reporter transfection Molecular endocrinology Medium 19608642
2012 IGF-1 inhibits GH gene expression by disrupting the POU1F1/CBP complex at the GH promoter; IGF-1 receptor signaling prevents CBP binding to the GH promoter (shown by ChIP), and a CBP S436A phosphorylation-dead mutant abolishes IGF-1 inhibition, elevating serum GH in knock-in mice. ChIP assay, luciferase reporter, CBP mutant (S436A) knock-in mouse model, serum GH/GHRH stimulation assay Molecular and cellular biology High 22890843
2012 POU1F1 directly binds multiple sites at the HSII region of the hGH LCR, confers robust POU1F1-dependent activation of hGH-N in a minichromosome model, and is required for POU1F1-dependent histone acetylation and methylation throughout the LCR/hGH-N domain; one binding site maps to the 3' UTR of a primate-specific LINE-1 retrotransposon. Minichromosome reporter system, in vitro DNA binding, ChIP for histone modifications, transfection assays Journal of molecular biology Medium 22094313
2015 POU1F1 Pro76Leu mutation (in the transactivation domain) selectively alters DNA-binding affinity at hGH-LCR and hGH1 sites (but not PRL sites), enhances interactions with cofactors PITX1, LHX3a, and ELK1 (by Co-IP), and causes dramatic loss of protein expression in homozygous knock-in mice despite normal mRNA levels. Bandshift (EMSA) assay, Co-immunoprecipitation, knock-in mouse model, immunoblotting Human molecular genetics High 26612202
2015 ERK (downstream of FGFR2) directly interacts with and phosphorylates POU1F1, increasing POU1F1 binding to the Mre11 promoter and repressing Mre11 expression, thereby decreasing double-strand break repair in breast cancer cells. Co-immunoprecipitation, phosphorylation assay, ChIP on Mre11 promoter, reporter assay, shRNA knockdown Human molecular genetics Medium 25788520
2019 POU1F1 (Pit-1) in breast tumor cells drives recruitment and M2 polarization of macrophages via transcriptional regulation of CXCL12 secretion; TAMs in turn promote tumor growth, angiogenesis, and lung metastasis. In vitro co-culture, zebrafish and mouse xenograft models, CXCL12 measurement, flow cytometry for macrophage markers, shRNA knockdown of POU1F1 The Journal of pathology Medium 31292963
2020 POU1F1 mediates ADTRP-induced transcription of TFPI by binding to a 50-bp ADTRP-response element (-806 to -756 bp upstream of TFPI TSS); knockdown of POU1F1 abolishes ADTRP-mediated TFPI transcription; direct binding confirmed by ChIP and EMSA. Luciferase reporter assay (large/small deletions), ChIP, EMSA, siRNA knockdown Gene Medium 32445923
2021 POU1F1 transcriptionally regulates the LDHA gene in breast cancer cells; POU1F1 overexpression increases LDHA expression and lactate production, promoting glycolytic reprogramming; LDHA knockdown in POU1F1-overexpressing cells reduces tumor volume and [18F]FDG uptake in xenograft mice. shRNA knockdown, overexpression, luciferase reporter, xenograft mouse model with PET imaging, human primary cancer cell cultures Oncogene Medium 33714987
2021 HMGA1B/2 transcriptionally activates POU1F1 in gastric cancer; POU1F1 in turn promotes CXCL12/CXCR4-dependent macrophage polarization; GST pull-down and Co-IP confirmed physical interaction between HMGA1B/2 and POU1F1; ChIP and dual luciferase assays confirmed HMGA1B/2 transcriptional regulation of POU1F1. GST pull-down, Co-immunoprecipitation, ChIP, dual luciferase reporter assay, xenograft mouse model Cell death & disease Medium 33927188
2021 The stem cell RNA-binding protein Musashi1 directly binds the Pou1f1 mRNA 3' UTR and exerts translational repression of POU1F1 in female somatotropes; leptin signaling is required to relieve this repression; Musashi immunoprecipitation from whole pituitary co-purifies Pou1f1 mRNA. RNA immunoprecipitation, translational reporter assay, Cre-LoxP Lepr-null somatotrope purification, immunocytochemistry, single-cell RNA-seq Endocrinology Medium 33373440
2021 Heterozygous missense POU1F1 variants that affect only the POU1F1 beta isoform retain repressor activity and shift splicing to favor the beta isoform, causing dominant-negative loss of function; identified by high-throughput splicing reporter assay testing 1,070 SNVs. High-throughput splicing reporter assay (1,070 variants), functional repressor activity assay, clinical co-segregation in multiple families American journal of human genetics High 34270938
2021 A POU1F1 intronic variant (c.143-69T>G in intron 1 of PIT-1α) shifts splicing to produce exclusively the PIT-1β transcript; the PIT-1β-Ile51Ser mutant protein represses PIT-1α transcriptional activity and abolishes transactivation of the rat PRL promoter in GH3 cells, causing CPHD. Gene splicing experiments, luciferase reporter assay, lymphocyte mRNA expression analysis European journal of endocrinology Medium 33886498
2022 The intronic Pou1f1 variant c.143-83A>G disrupts a branch site in the pre-mRNA, shifting splicing to decrease the alpha isoform, increase the beta isoform, and produce an exon-skipped transcript; homozygous knock-in mice show pituitary hypoplasia, somatotroph reduction, dwarfism, and IGF-1/T4 deficiency. Knock-in mouse model (CRISPR/genome engineering), RNA-seq, RT-PCR, immunohistochemistry, splicing analysis in cultured cells Endocrinology High 36427334
2016 Leptin signaling to somatotropes is required to maintain POU1F1 protein levels and all POU1F1-dependent hormones (GH, PRL, TSH); reduction is sex-dependent (occurs in females but not males for TSH and PRL), demonstrating a tropic role for leptin in controlling POU1F1-dependent cell lineages. Cre-LoxP conditional Lepr knockout in somatotropes, FACS-purified cell populations, enzyme immunoassays, qPCR Endocrinology Medium 27571135
2001 POU1F1 W193R missense mutation (in the fourth alpha-helix of the POU-specific domain) causes a ~500-fold reduction in DNA binding and transcriptional activation; a frameshift (747delA) removes the entire DNA recognition helix of the homeodomain, producing a nonfunctional protein. DNA-binding assay, transactivation reporter assay, cell transfection The Journal of clinical endocrinology and metabolism Medium 11297581
2023 Genetic epistasis between Pou1f1 and Six3 in mice: Six3 heterozygotes have pituitary dysmorphology; Six3+/-; Pou1f1+/dw double heterozygotes have a pronounced pituitary phenotype including pituitary growth through the palate, supporting digenic pituitary disease. Genetically engineered double-heterozygous mice, pituitary histology, phenotypic analysis Human molecular genetics Medium 35951005

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Cell 692 2902927
1989 Dissection of functional domains of the pituitary-specific transcription factor GHF-1. Nature 218 2574416
1990 Expression of GHF-1 protein in mouse pituitaries correlates both temporally and spatially with the onset of growth hormone gene activity. Cell 212 1690079
1991 Thyrotropin-releasing hormone regulation of human TSHB expression: role of a pituitary-specific transcription factor (Pit-1/GHF-1) and potential interaction with a thyroid hormone-inhibitory element. Proceedings of the National Academy of Sciences of the United States of America 125 1901656
1990 The homeodomain protein, Pit-1/GHF-1, is capable of binding to and activating cell-specific elements of both the growth hormone and prolactin gene promoters. Molecular endocrinology (Baltimore, Md.) 124 2284007
1993 GHF-1-promoter-targeted immortalization of a somatotropic progenitor cell results in dwarfism in transgenic mice. Genes & development 121 8096199
1989 Purification of growth hormone-specific transcription factor GHF-1 containing homeobox. Science (New York, N.Y.) 105 2563596
1988 Extinction of growth hormone expression in somatic cell hybrids involves repression of the specific trans-activator GHF-1. Cell 83 3167985
2005 Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency. The Journal of clinical endocrinology and metabolism 80 15928241
1993 The transcription factor Pit-1/GHF-1 is expressed in hemopoietic and lymphoid tissues. European journal of immunology 76 8458380
1995 M-phase-specific phosphorylation of the POU transcription factor GHF-1 by a cell cycle-regulated protein kinase inhibits DNA binding. Molecular and cellular biology 59 8524234
2008 OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters. The Journal of clinical endocrinology and metabolism 58 18628516
1995 Regulation of the pituitary-specific transcription factor GHF-1/Pit-1 messenger ribonucleic acid levels by growth hormone-secretagogues in rat anterior pituitary cells in monolayer culture. Endocrinology 55 7649093
1996 GHF-1/Pit-1 functions as a cell-specific integrator of Ras signaling by targeting the Ras pathway to a composite Ets-1/GHF-1 response element. The Journal of biological chemistry 54 8798730
2021 HMGA1B/2 transcriptionally activated-POU1F1 facilitates gastric carcinoma metastasis via CXCL12/CXCR4 axis-mediated macrophage polarization. Cell death & disease 50 33927188
1993 Pit-1/GHF-1 expression in pituitary adenomas: further analogy between human adenomas and rat SMtTW tumours. Journal of molecular endocrinology 50 8297469
1990 Sp1 can displace GHF-1 from its distal binding site and stimulate transcription from the growth hormone gene promoter. Molecular and cellular biology 47 2181288
2012 Insulin-like growth factor 1 mediates negative feedback to somatotroph GH expression via POU1F1/CREB binding protein interactions. Molecular and cellular biology 45 22890843
1999 Synergistic activation of the prolactin promoter by vitamin D receptor and GHF-1: role of the coactivators, CREB-binding protein and steroid hormone receptor coactivator-1 (SRC-1). Molecular endocrinology (Baltimore, Md.) 45 10406465
2021 POU1F1 transcription factor induces metabolic reprogramming and breast cancer progression via LDHA regulation. Oncogene 43 33714987
1999 A role for A/T-rich sequences and Pit-1/GHF-1 in a distal enhancer located in the human growth hormone locus control region with preferential pituitary activity in culture and transgenic mice. Molecular endocrinology (Baltimore, Md.) 42 10446901
2005 Functional relationship between LHX4 and POU1F1 in light of the LHX4 mutation identified in patients with pituitary defects. The Journal of clinical endocrinology and metabolism 41 15998782
2001 Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1/POU1F1 gene. The Journal of clinical endocrinology and metabolism 39 11297581
1995 Negative regulation of expression of the pituitary-specific transcription factor GHF-1/Pit-1 by thyroid hormones through interference with promoter enhancer elements. Molecular and cellular biology 38 7565785
1992 Nucleotide sequence of the complementary DNA for human Pit-1/GHF-1. Biochimica et biophysica acta 38 1370379
2021 High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency. American journal of human genetics 36 34270938
1992 Complementary DNA cloning and expression of Pit-1/GHF-1 from the domestic turkey. DNA and cell biology 34 1418622
2019 POU1F1 transcription factor promotes breast cancer metastasis via recruitment and polarization of macrophages. The Journal of pathology 33 31292963
1992 Structures of cDNAs encoding chum salmon pituitary-specific transcription factor, Pit-1/GHF-1. Gene 33 1634120
2010 PROP1, HESX1, POU1F1, LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Hormone research in paediatrics 32 20389107
2019 Relationship between SNPs of POU1F1 Gene and Litter Size and Growth Traits in Shaanbei White Cashmere Goats. Animals : an open access journal from MDPI 30 30934610
2015 Functional characterization of a human POU1F1 mutation associated with isolated growth hormone deficiency: a novel etiology for IGHD. Human molecular genetics 30 26612202
1999 The tissue-specific transcription factor Pit-1/GHF-1 binds to the c-fos serum response element and activates c-fos transcription. Molecular endocrinology (Baltimore, Md.) 29 10319324
1998 Role of GHF-1 in the regulation of the rat growth hormone gene promoter by thyroid hormone and retinoic acid receptors. The Journal of biological chemistry 29 9765286
1998 A direct protein-protein interaction is involved in the cooperation between thyroid hormone and retinoic acid receptors and the transcription factor GHF-1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 9737723
2002 Pit-1/GHF-1 and GH expression in the MCF-7 human breast adenocarcinoma cell line. The Journal of endocrinology 27 11927395
1996 Molecular cloning and characterization of the yellowtail GH gene and its promoter: a consensus sequence for teleost and avian Pit-1/GHF-1 binding sites. Journal of molecular endocrinology 26 8672234
1995 A novel pituitary transcription factor is produced by alternative splicing of the human GHF-1/PIT-1 gene. Gene 26 7721104
2003 New N-terminal located mutation (Q4ter) within the POU1F1-gene (PIT-1) causes recessive combined pituitary hormone deficiency and variable phenotype. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 24 12932747
1999 Changes in the levels of mRNAs for GH/prolactin/somatolactin family and Pit-1/GHF-1 in the pituitaries of pre-spawning chum salmon. Journal of molecular endocrinology 24 10514556
2019 A novel missense mutation (L280V) within POU1F1 gene strongly affects litter size and growth traits in goat. Theriogenology 23 31226610
2014 Molecular analysis of PROP1, POU1F1, LHX3, and HESX1 in Turkish patients with combined pituitary hormone deficiency: a multicenter study. Endocrine 22 25500790
2005 Absent or delayed adrenarche in Pit-1/POU1F1 deficiency. Hormone research 22 16210857
1993 Pit-1/GHF-1 binds to TRH-sensitive regions of the rat thyrotropin beta gene. Biochemistry 22 8364038
2002 Neonatal Meishan pigs show POU1F1 genotype effects on plasma GH and PRL concentration. Animal reproduction science 21 11812632
1995 Reconstitution of protein kinase A regulation of the rat prolactin promoter in HeLa nonpituitary cells: identification of both GHF-1/Pit-1-dependent and -independent mechanisms. Molecular endocrinology (Baltimore, Md.) 21 7659093
2016 A Sex-Dependent, Tropic Role for Leptin in the Somatotrope as a Regulator of POU1F1 and POU1F1-Dependent Hormones. Endocrinology 20 27571135
2003 The de novo Q167K mutation in the POU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient. Pediatric research 20 12904605
2015 FGFR2 regulates Mre11 expression and double-strand break repair via the MEK-ERK-POU1F1 pathway in breast tumorigenesis. Human molecular genetics 19 25788520
2004 A new single nucleotide polymorphism in the chicken pituitary-specific transcription factor (POU1F1) gene associated with growth rate. Animal genetics 19 15265078
2016 Identification of Novel PROP1 and POU1F1 Mutations in Patients with Combined Pituitary Hormone Deficiency. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 27756091
2002 Lack of association of GH1 and POU1F1 gene variants with meat production traits in Piemontese cattle. Animal genetics 18 11849139
2012 Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency. Clinical endocrinology 17 22010633
2008 GHRH proliferative action on somatotrophs is cell-type specific and dependent on Pit-1/GHF-1 expression. Journal of cellular physiology 17 17941086
2007 A novel germline mutation, IVS4+1G>A, of the POU1F1 gene underlying combined pituitary hormone deficiency. Hormone research 17 18059085
1995 Retinoic acid induces expression of the transcription factor GHF-1/Pit-1 in pituitary prolactin- and growth hormone-producing cell lines. Endocrinology 17 7588287
2013 POU1F1 is a novel fusion partner of NUP98 in acute myeloid leukemia with t(3;11)(p11;p15). Molecular cancer 16 23332017
2008 A PstI polymorphism at 3'UTR of goat POU1F1 gene and its effect on cashmere production. Molecular biology reports 16 18654839
2006 Effect of genetic variations of the POU1F1 gene on growth traits of Nanyang cattle. Yi chuan xue bao = Acta genetica Sinica 16 17046590
2016 A novel heterozygous intronic mutation in POU1F1 is associated with combined pituitary hormone deficiency. Endocrine journal 15 27885216
2012 Analysis of polymorphism within POU1F1 gene in relation to milk production traits in dairy Sarda sheep breed. Molecular biology reports 15 22311029
1998 The LIM homeobox protein mLIM3/Lhx3 induces expression of the prolactin gene by a Pit-1/GHF-1-independent pathway in corticotroph AtT20 cells. FEBS letters 15 9714537
2021 Control of the Anterior Pituitary Cell Lineage Regulator POU1F1 by the Stem Cell Determinant Musashi. Endocrinology 14 33373440
2008 A proline-to-histidine mutation in POU1F1 is associated with production traits in dairy cattle. Animal genetics 14 18557974
2006 Identification and functional analysis of the novel S179R POU1F1 mutation associated with combined pituitary hormone deficiency. The Journal of clinical endocrinology and metabolism 14 16968807
2010 The Pit-1/Pou1f1 transcription factor regulates and correlates with prolactin expression in human breast cell lines and tumors. Endocrine-related cancer 13 19808898
2006 Ovis aries POU1F1 gene: cloning, characterization and polymorphism analysis. Genetica 13 16636924
2001 The turkey transcription factor Pit-1/GHF-1 can activate the turkey prolactin and growth hormone gene promoters in vitro but is not detectable in lactotrophs in vivo. General and comparative endocrinology 13 11589626
1998 Anterior pituitary development and Pit-1/GHF-1 transcription factor. Cellular and molecular life sciences : CMLS 13 9817984
2014 Polymorphism of sheep POU1F1 gene exon 6 and 3'UTR region and their association with milk production traits. Iranian journal of veterinary research 12 27175126
2006 Identification and characterization of four splicing variants of ovine POU1F1 gene. Gene 12 16942842
2020 ADTRP regulates TFPI expression via transcription factor POU1F1 involved in coronary artery disease. Gene 11 32445923
2020 Proteomic and Transcriptomic Analysis Identify Spliceosome as a Significant Component of the Molecular Machinery in the Pituitary Tumors Derived from POU1F1- and NR5A1-Cell Lineages. Genes 11 33261069
2012 Research resource: A genome-wide study identifies potential new target genes for POU1F1. Molecular endocrinology (Baltimore, Md.) 11 22638072
2011 A novel POU1F1 mutation (p.Thr168IlefsX7) associated with an early and severe form of combined pituitary hormone deficiency: functional analysis and follow-up from infancy to adulthood. Clinical endocrinology 11 21521297
2011 Homozygous microdeletion of the POU1F1, CHMP2B, and VGLL3 genes in chromosome 3--a novel syndrome. American journal of medical genetics. Part A 11 21815258
1997 Molecular cloning of gilthead seabream (Sparus aurata) pituitary transcription factor GHF-1/Pit-1. Gene 11 9034317
2018 Precocious or early puberty in patients with combined pituitary hormone deficiency due to POU1F1 gene mutation: case report and review of possible mechanisms. Hormones (Athens, Greece) 10 30460459
2012 Identification of a novel mutation in the exon 2 splice donor site of the POU1F1/PIT-1 gene in Japanese identical twins with mild combined pituitary hormone deficiency. Clinical endocrinology 10 21722153
2012 Polymorphisms and expression of the chicken POU1F1 gene associated with carcass traits. Molecular biology reports 10 22722987
2009 Associations of a HinfI PCR-RFLP of POU1F1 gene with growth traits in Qinchuan cattle. Animal biotechnology 10 19370456
2009 A novel recessive splicing mutation in the POU1F1 gene causing combined pituitary hormone deficiency. Journal of endocrinological investigation 10 19498317
2005 Three novel mutations in POU1F1 in Israeli patients with combined pituitary hormone deficiency. Journal of pediatric endocrinology & metabolism : JPEM 10 15844473
2005 MspI polymorphisms in the 3rd intron of the swine POU1F1 gene and their associations with growth performance. Journal of applied genetics 10 16110185
2023 Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man. Human molecular genetics 9 35951005
2016 Pou1f1, the key transcription factor related to somatic growth in tilapia (Orechromis niloticus), is regulated by two independent post-transcriptional regulation mechanisms. Biochemical and biophysical research communications 9 28013048
2001 Cloning of the full length pig PIT1 (POU1F1) CDNA and a novel alternative PIT1 transcript, and functional studies of their encoded proteins. Animal biotechnology 9 11370678
2021 POU1F1 mutations in combined pituitary hormone deficiency: differing spectrum of mutations in a Western-Indian cohort and systematic analysis of world literature. Pituitary 8 33742319
2021 A mutation of the β-domain in POU1F1 causes pituitary deficiency due to dominant PIT-1β expression. European journal of endocrinology 8 33886498
2011 Polymorphisms of caprine POU1F1 gene and their association with litter size in Jining Grey goats. Molecular biology reports 8 21769479
2011 Short communication: expression and alternative splicing of POU1F1 pathway genes in preimplantation bovine embryos. Journal of dairy science 8 21787958
2021 Intronic variant in POU1F1 associated with canine pituitary dwarfism. Human genetics 7 33550451
2012 Identification of novel SNPs in the Sarda breed goats POU1F1 gene and their association with milk productive performance. Molecular biology reports 7 23184007
2011 Congenital hypopituitarism due to POU1F1 gene mutation. Journal of the Formosan Medical Association = Taiwan yi zhi 7 21316014
2011 POU1F1-mediated activation of hGH-N by deoxyribonuclease I hypersensitive site II of the human growth hormone locus control region. Journal of molecular biology 7 22094313
2009 Expression of the synaptotagmin I gene is enhanced by binding of the pituitary-specific transcription factor, POU1F1. Molecular endocrinology (Baltimore, Md.) 7 19608642
2007 Polymorphisms in intron 1 of the porcine POU1F1 gene. Journal of applied genetics 7 17998594
2022 POU1F1/Pou1f1 c.143-83A > G Variant Disrupts the Branch Site in Pre-mRNA and Leads to Dwarfism. Endocrinology 6 36427334
2021 Congenital hypopituitarism due to novel compound heterozygous POU1F1 gene mutation: A case report and review of the literature. Molecular genetics and metabolism reports 6 34815942
2019 Characterization of a Novel POU1F1 Mutation Identified on Screening 160 Growth Hormone Deficiency Patients. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 6 31022740

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