FOXE1 source guide

This guide separates original annotation references from auxiliary donor or corroborating sources. Selected Methods, Results and captions are identified for each paper. Access to an article does not imply that every section, supplement or figure image was examined. Authentic abstract-only sources remain explicitly limited; a source-specific unresolved assertion is not a claim that the paper concerns the wrong gene.

No new publication quotations are proposed. Experimental species, insert identity, host cells, fragments and alleles are kept distinct. The source assessment and original GOA evidence code describe different things: independently read corroboration does not replace an original source assertion.

PMID:12165566

PubMed; DOI; Original source 1

Original annotation reference. Indexed publisher PDF text, selected Results/Methods/Figures 4–5 captions; no figure pixels or supplements. Human WT genomic FOXE1 and S57N constructs were sequence-checked. Equal in-vitro translation and 293-EBNA nuclear extracts support sequence-specific TG-site binding; anti-FLAG supershift distinguishes the target complex. WT activates a concatemerized rat-TPO-site/TK reporter, while S57N retains reduced binding and partial activation. Two homozygous human siblings had extensive hard and soft palate clefts and thyroid agenesis. The reporter is synthetic and contains rat promoter sites; this is not endogenous human promoter occupancy. Patient phenotype, biochemical activity and developmental cell autonomy are distinct. Do not describe S57N as complete loss or map historical construct length to a natural-product suffix.

Locators: Publisher extraction Results 29–35,98–103; captions 121–123,138–139; Methods 165–175

PMID:16882747

PubMed; DOI; Original source 1

Original annotation reference. Indexed publisher PDF text, selected Methods/Results and Figure 2 caption; no pixel or supplement inspection. Human WT genomic sequence and R102C mutant were tested by equal in-vitro translation/TG-probe EMSA and by human TPO −366/+50 promoter reporter in 293-EBNA cells with TTF1 coexpression. WT binds and activates; R102C has negligible binding and activity. The affected child has nonfunctional thyroid tissue in a eutopic location. Do not universalize thyroid agenesis across FOXE1 variants or call this purified equilibrium binding. The paper describes a historical 367-aa protein, whereas current official sequence is 373 aa; exact allele sequence was not reconstructed.

Locators: Methods 51–56; Results 67,72–74; Figure 2 caption 145–146

PMID:20094846

PubMed; DOI; Original source 1

Original annotation reference. Original journal article text uploaded by author Maslinda Musa, selected Methods/Results/Discussion/Figures 3–4 captions; no pixels or supplements. Human normal-control and patient N132D genomic inserts were sequence-checked in pcDNA3.1/V5/His-TOPO. HepG2 nuclear-extract EMSA uses a TG promoter probe and unlabeled competition. A separate 416-bp human TPO promoter reporter responds to WT and N132D. N132D also occurs in unaffected relatives, and the authors do not conclude it causes dysgenesis. Abstract/Results shorthand calls the DNA-binding target TPO, but Methods and Figure 3 identify TG. Results describes 5% loss whereas Discussion says 0.5-fold loss; retain the discrepancy and do not synthesize a precise percentage. Host nuclear extracts are not purified protein; no natural-product mapping.

Locators: Author upload 91–98; Methods 371–516; Results 518–628; Figure 3 caption 653–678; Figure 4 caption 754–763; Discussion 769–785

PMID:20484477

PubMed; DOI; Original source 2

Original annotation reference. Authentic PubMed abstract read. Publisher PDF URL returns purchase/minimal HTML; author page offers request-only full text. Abstract reports human homozygous F137S through maternal chromosome 9 isodisomy, failed DNA binding and negligible transfection activity. Exact original constructs, promoter substrates and controls were not inspected. Do not substitute another mutation paper or the conference abstract for this journal experiment.

Locators: PubMed structured abstract; publisher minimal page; ResearchGate request-only page

PMID:24219130

PubMed; DOI; Original source 1

Original annotation reference. Actual PMC original selected Methods/Results/captions recovered through indexed search, despite direct-page challenge and failed XML/BioC requests. No full-download or pixel claim. Human WT and R73S FOXE1 are compared in HEK293 with human TG/TPO reporters, with and without PAX8/NKX2-1. EMSA detects no binding difference. R73S increases reporter activity with matched protein abundance in HEK293. In primary human thyrocytes, endogenous TG protein abundance increases by Western blot, TPO does not increase (data not shown), and mutant FOXE1 abundance is higher. Primary-thyrocyte result does not isolate per-molecule transactivation from protein abundance. Abstract and Results swap the 1.5/1.7 promoter fold labels; no precise fold attribution used. The phenotype is not evidence that R73S is another loss-of-function allele.

Locators: Patients and Methods / functional characterization; Results / functional characterization; Figures 1D,2,3 captions

PMID:27852061

PubMed; DOI; Original source 1

Original annotation reference. Authentic full XML selected paragraphs 10,12–16,18,21–22,29,32–33,42–43,48–52,54–55; no pixels or supplements. Human thyroid endogenous and tagged co-immunoprecipitation, array and mammalian two-hybrid support ELK1 association. Two-hybrid uses FOXE1 residues 164–373; full-length protein is used in other assays. Promoter effects are context/polyalanine dependent. TERT DNA-complex shifts require ELK1; ChIP detects promoter association. Do not equate TERT ChIP with direct FOXE1 motif contact or affinity-isolated HEK293 proteins with a pure binary equilibrium assay. ELK1 truncation association may involve endogenous bridging. Results and Figure 1D reverse IP/blot orientation, and paragraph 32 repeats ELK1 in prose; use actual Methods/Figure 5 for coexpression details. No splice-product equivalence.

Locators: PMC XML paragraph indices 10, 12–16, 18, 21–22, 29, 32–33, 42–43, 48–52, 54–55; Figures 1, 2, 4, 5 captions and Methods.

PMID:28473536

PubMed; DOI; Original source 2

Original annotation reference. Retained original text selected protein-expression/HT-SELEX/methyl-SELEX Methods and Results, plus original workbook target rows and PWM blocks. FOXE1 eDBD residues 31–164 (134 aa) exactly matches current official sequence. Original workbook contains separate methyl-HT-SELEX and HT-SELEX motifs for this target. Bacterially expressed affinity-tagged domains were selected against randomized DNA ligands. No full-length FOXE1, endogenous chromatin occupancy, methylation-dependent cellular regulation, atomic structure or measured affinity is established by this target-specific motif record.

Locators: S1 row 263; S2 rows 5018–5027/9124; main protein-expression and HT/methyl-SELEX Methods

PMID:9169137

PubMed; DOI; Original source 2

Original annotation reference. PubMed abstract and publisher article preview read; DOI open failed and publisher requires purchase. Human cDNA isolation, mapping and a predicted forkhead-domain protein are reported. The abstract discusses family developmental roles and a historical 376-aa clone. No actual target-specific morphogenesis experiment has been inspected. A family statement or alanine-rich sequence does not by itself establish a human developmental mechanism or repression assay. Do not infer wrong citation from incomplete text.

Locators: PubMed abstract and publisher preview

PMID:9697705

PubMed; DOI; Original source 1

Original annotation reference. Original Nature Genetics article text, selected Methods/Results/Figures 3–4 captions through indexed author-copy page; no pixels or supplements. Human normal-control and patient A65V coding inserts were sequence-checked. WT binds a TG oligonucleotide in translated lysate and transfected 293 nuclear extracts with anti-FLAG supershift; A65V has negligible binding despite comparable nuclear abundance. WT activates a synthetic 16-site rat-TPO/TK reporter; mutant has negligible activity. Two affected siblings have thyroid agenesis and craniofacial anomalies. Nuclear fraction recovery supports nuclear access, not exclusive endogenous localization. Reporter sites are rat-derived and synthetic. No purified affinity, exact current natural-product mapping or general all-variant null claim.

Locators: Results 267–331; Figure 3 caption 401–409; Methods 431–524

PMID:21177256

PubMed; DOI; Original source 1

Original annotation reference. Original author-uploaded 10-page journal PDF text retrieved through web tool after publisher/relative-link failures. Selected Methods/Results and captions read; figure pixels and supplements not inspected. Human genomic FOXE1 was cloned into pcDNA3.1/V5-His; WT and mutant constructs were sequence-checked. Experiments use 293 EBNA cells. MSX1/TGFB3 RNA/protein and promoter reporters increase after WT FOXE1 overexpression. Nuclear-extract EMSA includes anti-V5 supershift, competitor and mutated-probe controls; anti-V5 ChIP assays overexpressed protein on endogenous promoter chromatin. E14 C57BL/6 Foxe1-null versus heterozygous embryos show reduced Msx1 dental-mesenchymal and Tgfb3 anterior-palatal epithelial transcripts. Nuclear-extract recovery supports nuclear access; no microscopy or exclusive-localization claim. This is not purified affinity, native human palate perturbation or endogenous untagged ChIP. Do not equate mutant/polymorphism constructs with independently mapped natural products.

Locators: Methods: PDF pages 6–7, lines 391–428 constructs,429–437 reporters,472–519 ChIP/EMSA,531–602 mouse/ISH Results: PDF pages 1–2, lines 78–188; page 3 lines 203–205 captions: Figures 3–6, pages 3–5

PMID:15494458

PubMed; DOI; Original source 1

Original annotation reference. Selected original author-hosted journal text, Methods/Results/Discussion and captions read through indexed response; no figure pixels or supplementary data. Human tissues span CS14, CS15, CS19 and fetal 9/11 developmental weeks. FOXE1 was measured by radiolabeled in-situ RNA probes generated from a human genomic 203-bp region, with sense controls. FOXE1 signal begins at CS15 in thyroid, occurs in CS19 thymus/oropharyngeal epithelium, and later tracheal/esophageal epithelium. Thyroglobulin immunostaining is a separate protein assay. Developmental expression is observed, not a FOXE1 perturbation or direct mechanistic test. The authors leave the functional significance of thymic expression unresolved; mouse knockout biology is background comparison. Do not import PAX8 kidney or TITF1 brain/lung findings onto FOXE1.

Locators: Methods: Indexed lines 278–432 Results: 646–698 captions: Figure 1 lines 573–588; Figure 3 lines 781–793 Discussion: 727–747 and 1031–1057

PMID:9214635

PubMed; DOI; Original source 1

Auxiliary donor or corroborating source. Original author-uploaded EMBO article text, selected rat cloning/HeLa binding/repression/FRTL5 insulin and Methods; no pixels or supplements. Rat thyroid cDNA encodes the assayed TTF2. Transfected HeLa extracts bind and footprint TG/TPO sites. Rat TTF2 suppresses TTF1-driven TG and PAX8-driven TPO reporters, including promoters with altered TTF2 sites, while CMV and a synthetic TTF1-driven control remain unaffected. FRTL5 RNA expression responds to insulin withdrawal/readdition. Mouse developmental expression is a separate assay. Human HeLa host is not human protein. Repression is promoter-specific and can occur without the cognate site; this does not establish a DNA-bound repressor mechanism. Insulin-induced transcript abundance does not independently identify every downstream step of an insulin response.

Locators: Original EMBO article: cloning lines 263–370 and Figure 3 caption 406–418; insulin Results 555–581; repression Results 612–663 and Discussion 787–833; Methods 1034–1151. Line numbers refer to the article-specific indexed extraction, not a concatenated multi-article response.

PMID:9697704

PubMed; DOI; Original source 1

Auxiliary donor or corroborating source. Original author-uploaded Nature Genetics article text, selected knockout Results/Methods/captions; no pixels or supplements. Mouse Titf2-null embryos form a bud but fail normal descent; some lose thyroid precursors and others retain small ectopic glands that express thyroglobulin. Newborn blood has impaired FT4 and compensatory TSH. Cleft palate is observed. The authors report normal-appearing thymus and other structures, some as data not shown. Hormone output and organ development are measured, not FOXE1 catalysis of hormone chemistry. Normal thymus appearance is bounded mouse evidence, not refutation of human expression. Preserve the exact mouse donor and human ISS source.

Locators: Results 193–326; Figure 1 caption 327–336; Methods 458–523/572–583

PMID:15581879

PubMed; DOI; Original source 1

Auxiliary donor or corroborating source. Original journal PDF text from Max Planck repository, selected animal/targeting Methods and Foxe1 migration Results; no pixels or supplements. Mouse Foxe1 deletion and spatially restricted rescue support thyroid-bud migration. The rescue construct explicitly inserts rat Foxe1 coding sequence NM138909 into the mouse Titf1 locus; it restores bud migration when surrounding pharyngeal endoderm lacks Foxe1. This is mouse loss plus rat-cDNA rescue, not direct human functional evidence or a pure mouse-protein rescue. It establishes a developmental program and spatial competence, not direct physical movement by a transcription factor. Foxe1-deprived Pax8-null buds can also migrate, with residual-expression/compensation explanations left open.

Locators: Methods 55–97; Results 358–428 and discussion of migration

PMID:15367491

PubMed; DOI; Original source 1

Auxiliary donor or corroborating source. Original HMG journal PDF text via CiteSeerX, selected mouse skin/graft Results and Methods, human BCC expression and captions; no pixels or supplements. Foxe1-null newborn skin grafted to immunodeficient mice generates abnormally oriented, thin/curly hairs. Early newborn morphology is similar; later follicular growth/orientation is altered despite conserved lineage markers. Separate human BCC immunostaining and rat-promoter/Gli reporter assays are present. Do not transfer Gli2 acting on the Foxe1 promoter into FOXE1 DNA-target activity. Skin grafts reduce systemic-hypothyroidism confounding but do not establish an isolated cell-autonomous human mechanism. Mouse loss, human expression and rat promoter assays remain separate.

Locators: Results 167–237/315–355/473–512; Methods 756–825; Figure 4 caption 444–468

PMID:9287345

PubMed; DOI

Auxiliary donor or corroborating source. Authentic PubMed abstract read; JBC full-text route robots-denied. Not an exact current rat GOA donor citation in the captured snapshot. Abstract reports TSH/insulin/IGF1 regulation of FRTL5 TTF2 RNA and transcription rate. Background corroboration only. Do not claim original Methods inspected or replace the exact current donor reference 9214635.

Locators: PubMed abstract

PMID:22304410

PubMed; DOI; Original source 1; Original source 2

Auxiliary donor or corroborating source. Authentic Europe PMC original XML recovered after direct-page challenges. Selected Methods, Results, captions and Discussion read; no figure pixels or supplements. The pBROAD3 construct uses the mouse ROSA26 promoter and an explicitly mouse TTF2 coding insert. Pronuclear transgenesis, PCR/Southern confirmation, palatal RNA/protein and immunohistochemistry accompany cleft-palate observations. Controls show changing expression during E12.5–E15.5; the transgene disrupts that temporal pattern and is associated with persistent medial-edge epithelial expression and unfused shelves. Broad transgenic overexpression is distinct from endogenous loss or cell-specific rescue. The authors leave effects on apoptosis, EMT and migration for future work; none is measured as a downstream mechanism here. Results and Discussion differ over E13.5 significance, so no uniform all-stage increase is asserted. This mouse study does not directly assay human FOXE1; the separate 21177256 loss experiment remains independently attributed.

Locators: XML paragraph indices 9–18 Methods; 19–35 Results/captions; 39–43 Discussion

Donor and phylogenetic scope

The 10 donor projections preserve the exact original human source objects, the complete captured rat and mouse annotation lists, and the actual donor relations. Current same-term matches are distinguished from separately labeled related-term evidence. Raw context 39 has no exact same-term match in the captured rat list; raw context 40 has related GO:0000122 evidence that is not silently substituted for the original GO:0045892 assertion. A missing current match does not disprove a historical or alternate Ensembl source.

All six incoming IBAs descend from positive PTN000930906 assertions on the actual human O00358 lineage in PTHR11829. The target MSA sequence matches the official 373-aa protein. Two fungal negative records lie outside that human lineage. Original and current source lists are separately dated; self-donor evidence is legitimate and donor count is not an evidential ranking.

Ontology scope

Five redundancy comparisons use is_a ancestry. The thyroid-development to system-development comparison instead follows GO:0030878 part_of GO:0035270 is_a GO:0048731. That part-whole path supports overlapping developmental coverage without asserting a pure subclass relationship. ELK1’s established Pol II-specific DNA-binding TF class supports GO:0061629, a specific child of GO:0140297; the cellular interaction assays do not become purified-interface measurements through this refinement.

Source availability and preparation limits

The review uses 17 publications and three PTHR11829 family files. Fresh ownership checks preceded acquisition. The three family files and PMID:28473536 were reused byte-for-byte from main; the other 16 publications were genuinely fetched. The normal cache access flags below describe the retrieved files. Separately linked selected primary readings remain the basis for the source-specific assay judgments; an abstract-only cache does not erase those independently recorded readings.

Normal publication cache access

Review follow-up: term granularity and source verification

All eight original GO:0043565 rows now share the gene-level TOO_GENERAL judgment because retained GO:0000978 entails sequence-specific DNA binding. The six directly inspected binding experiments retain their source-specific findings and assay limits. The F137S paper remains unverified beyond its authentic abstract; its granularity judgment does not claim inspection of the original probe, constructs or controls.

The original F137S Pol II transcription-factor and regulation rows are accepted as established gene-level capacities, with independent reference-only support from the inspected human studies listed above. The original cloning-paper morphogenesis row is retained as non-core using independent human and mouse developmental evidence. PMID:20484477 and PMID:9169137 keep their UNVERIFIED reference assessments and disclosed access limits. No unseen experiment is certified.

The directional transcription rows are refined to GO:0045944 and GO:0000122. The former rests on human WT FOXE1 activation of the rat-TPO-site/TK reporter in PMID:9697705; the latter retains the rat-insert/human-host distinction and promoter-specific repression in PMID:9214635. Their original source identifiers and evidence codes remain unchanged. The selected Methods/Results and caption locators above remain the basis for these interpretations.

The insulin-response row remains undecided: the exact historical transfer and alternate Ensembl source are unresolved, and transcript induction alone does not settle FOXE1’s functional role in that response. Broader donor relations are reported as context limits; their difference from a human transfer does not by itself establish a source error or a corrected relation. No new source-defect record or thyroid-hormone-generation annotation is added.

Evidence continues to use reference-only citations under the campaign’s explicit no-new-quotations instruction. The source guide provides public primary URLs, selected locators and access limits. This does not claim verbatim-quote validation or full-text access beyond the declared scope.