Affinage

GFI1B

Zinc finger protein Gfi-1b · UniProt Q5VTD9

Length
330 aa
Mass
37.5 kDa
Annotated
2026-06-10
76 papers in source corpus 36 papers cited in narrative 36 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

GFI1B is a SNAG-domain, zinc-finger transcriptional repressor that orchestrates erythroid, megakaryocytic, and stem/progenitor cell fate by silencing lineage-inappropriate gene programs (PMID:11825872, PMID:24711581). It represses targets by binding high-affinity Gfi1/Gfi1b consensus sites through its C-terminal zinc fingers and recruiting a corepressor module—CoREST, the histone demethylase LSD1, and HDAC1/2—via its N-terminal SNAG domain, driving loss of activating H3K4 methylation at target promoters (PMID:17707228). SNAG-dependent recruitment of the LSD1-CoREST complex requires dimethylation of SNAG lysine 8, and a short p32 isoform lacking the first two zinc fingers engages this complex more efficiently than the major p37 isoform (PMID:22399799). GFI1B additionally docks histone methyltransferases SUV39H1 and G9A at pericentric heterochromatin to deposit repressive H3K9 methylation (PMID:16688220), and forms a tripartite complex with beta-catenin and LSD1 to modulate Wnt/TCF-dependent transcription (PMID:30894540). Direct targets span cell-cycle and lineage regulators including p21WAF1 (PMID:9566867), the oncogene Meis1 (PMID:23308270), TGFBR3 (PMID:20124515), SPI1/PU.1 (PMID:26851695), and embryonic globin genes (PMID:24800817), and GFI1B participates in interlocking autoregulatory circuits—auto-repressing its own promoter and cross-repressing GFI1, the latter partly through protein interaction with GATA-1 rather than direct DNA binding (PMID:15718298, PMID:16177182). Genetically, GFI1B is required at an early bipotent erythro-megakaryocytic progenitor stage and again at a promegakaryocyte stage (PMID:24711581), and acts downstream of RUNX1 to drive the endothelial-to-hematopoietic transition (PMID:22668850, PMID:38961746). Dominant-negative truncating mutations in the zinc-finger DNA-binding domain (e.g. Q287*, G272fs) abolish DNA binding yet sequester the LSD1-RCOR-HDAC complex away from normal targets, causing inherited gray platelet syndrome and macrothrombocytopenic bleeding disorders (PMID:24325358, PMID:30655368, PMID:27122003).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Established GFI1B as a sequence-specific transcriptional repressor with a defined direct target, answering whether it acts on DNA and what biological process it controls.

    Evidence Reporter assays, promoter deletion/mutagenesis, and forced expression of repressor-domain mutants in IL-6-treated M1 myeloid cells, mapping a high-affinity site in the p21WAF1 promoter

    PMID:9566867

    Open questions at the time
    • Did not identify the corepressor machinery mediating repression
    • Restricted to a single target gene and a myeloid context
  2. 2002 High

    Genetically defined GFI1B as essential and lineage-specific in vivo, resolving which hematopoietic lineages depend on it.

    Evidence Constitutive knockout mice with chimera, histological, and flow cytometric analysis showing arrest of erythroid/megakaryocytic precursors and normal myelopoiesis

    PMID:11825872

    Open questions at the time
    • Embryonic lethality precluded analysis of adult-stage requirements
    • Did not distinguish direct transcriptional targets from secondary effects
  3. 2004 Medium

    Identified the first direct transcriptional targets and autoregulatory architecture, framing how GFI1B controls its own and GFI1 expression.

    Evidence EMSA, reporter assays, and ChIP in primary thymocytes and a human T-cell line for GFI1 cross-repression; EMSA/ChIP showing GATA-1 plus NF-Y activate the GFI1B promoter

    PMID:15131254 PMID:15280509

    Open questions at the time
    • Did not establish the corepressor complex used for autoregulation
    • Promoter regulation studied largely in reporter/cell-line contexts
  4. 2005 High

    Distinguished DNA-binding-dependent from protein-interaction-dependent repression by GFI1B, refining its regulatory logic at the GFI1B locus.

    Evidence EMSA, ChIP, reporter assays, and Co-IP in transgenic mice showing direct auto-/cross-repression and GATA-1-interaction-mediated suppression

    PMID:15718298 PMID:16177182

    Open questions at the time
    • Mechanism of how GFI1B-GATA-1 interaction blocks GATA-1 activation not structurally resolved
    • Tissue-restricted silencing (spleen vs bone marrow) left unexplained
  5. 2006 High

    Defined the SNAG domain as the indispensable effector module and linked GFI1B to heterochromatin-modifying enzymes, addressing how repression is enacted at chromatin.

    Evidence SNAG-mutant and locus-swap knock-in mice; Co-IP with SUV39H1/G9A plus ChIP and immuno-FISH at gamma-satellite and target promoters

    PMID:16397623 PMID:16688220

    Open questions at the time
    • Did not yet define the full SNAG-recruited corepressor complex
    • Relative contributions of H3K9 methyltransferases vs other cofactors to target repression unclear
  6. 2007 High

    Identified the core SNAG-recruited corepressor complex (CoREST/LSD1/HDAC1-2) and demonstrated its genome-wide functional requirement, defining the principal repression machinery.

    Evidence Affinity purification of GFI1B complexes, reciprocal Co-IP, genome-wide ChIP, and LSD1 knockdown showing target derepression with gained H3K4 methylation; GATA-1-mediated recruitment to Bcl-xL

    PMID:17420275 PMID:17707228

    Open questions at the time
    • Did not define how SNAG selects between cofactor complexes
    • Dynamics of complex assembly/disassembly during differentiation only partially addressed
  7. 2010 Medium

    Connected GFI1B repression to a defined signaling output, showing it tunes erythro-megakaryocytic differentiation through TGF-beta signaling.

    Evidence GFI1B knockdown in human progenitors, ChIP defining TGFBR3 as a direct target, phospho-Smad2 and Smad2/TIF1-gamma Co-IP analysis

    PMID:20124515

    Open questions at the time
    • Causal chain from TGFBR3 repression to lineage outcome not fully isolated
    • Single knockdown system
  8. 2012 High

    Defined isoform- and post-translational-modification control of corepressor recruitment, explaining how SNAG dimethylation licenses LSD1-CoREST binding.

    Evidence Isoform-specific Co-IP of p32/p37 with LSD1-CoREST, SNAG K8 mutagenesis, and isoform knockdown with erythroid differentiation readouts; RUNX1 dependence and EHT analysis in embryos

    PMID:22399799 PMID:22668850

    Open questions at the time
    • Enzyme(s) responsible for SNAG K8 dimethylation not identified
    • Quantitative impact of isoform ratio on target selection unresolved
  9. 2013 Medium

    Established the dominant-negative disease mechanism and lineage-specific direct targets, linking zinc-finger truncations to inherited platelet disorders.

    Evidence Patient mutation analysis with reporter assays for Q287* and fifth-zinc-finger frameshift dominant-negative activity; ChIP/reporter defining Meis1 as an erythroid-specific direct target

    PMID:23308270 PMID:23927492 PMID:24325358

    Open questions at the time
    • Molecular basis of dominant-negative interference (sequestration vs DNA squelching) not yet pinpointed
    • Reporter-based functional assays in cell lines
  10. 2014 High

    Resolved continuous adult-stage requirements and genome-wide repressive function, refining when and what GFI1B controls in steady-state hematopoiesis.

    Evidence Inducible conditional knockout in adult mice with stage-specific arrest, genome-wide ChIP/expression analysis, and globin-switching analysis in conditional knockouts

    PMID:24711581 PMID:24800817

    Open questions at the time
    • Mechanism of stage-specific target selectivity not defined
    • Sox6 as the globin-switching intermediary inferred, not directly proven as a GFI1B target
  11. 2016 Medium

    Pinned the dominant-negative defect to abolished DNA binding with retained interference, and connected GFI1B to cytoskeletal/lineage-balance programs, broadening the mechanistic picture of platelet disease.

    Evidence EMSA/reporter/dominant-negative assays in megakaryocytes for patient mutations; ChIP defining Kindlin3/Talin1 and SPI1 as targets; isoform CRISPR editing; Rgs18 signaling axis analysis

    PMID:26567214 PMID:26851695 PMID:27122003 PMID:27486782 PMID:27768697

    Open questions at the time
    • Whether all phenotypes flow through a single complex-sequestration mechanism unresolved
    • Individual target contributions to platelet defects not separated in vivo
  12. 2019 High

    Identified the LSD1-RCOR-HDAC complex as the primary GFI1B partner in megakaryoblasts and revealed a beta-catenin/GFI1B/LSD1 tripartite complex, unifying the disease mechanism and a Wnt-activating function.

    Evidence Co-IP/proteomics, patient iPSC-derived megakaryocyte modeling, pharmacological LSD1-GFI1B disruption; reciprocal Co-IP, ChIP-seq co-occupancy, TCF reporters, and Wnt3a rescue

    PMID:30655368 PMID:30894540

    Open questions at the time
    • How GFI1B switches between repressive and TCF-activating modes not mechanistically defined
    • Stoichiometry and assembly order of the tripartite complex unknown
  13. 2024 Medium

    Demonstrated that the GFI1B-LSD1 axis represses myeloid programs during megakaryopoiesis and acts at a temporally distinct EHT step, sharpening how interaction loss causes lineage skewing.

    Evidence Transcriptomics of multiple patient variants in MEG01, scRNA-seq of iPSC-derived megakaryocytes, ectopic GFI1B in hemogenic endothelium, and pharmacological LSD1 inhibition

    PMID:38548886 PMID:38961746

    Open questions at the time
    • Direct myeloid-gene targets responsible for repression not all defined
    • Temporal switch between GFI1B-dependent and LSD1-dependent EHT steps not molecularly resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GFI1B selects among its cofactor complexes (LSD1-CoREST-HDAC, SUV39H1/G9A, beta-catenin) and switches between repressive and activating outputs across lineages and developmental stages remains unresolved.
  • No structural model of the SNAG-corepressor interface or its regulation by K8 dimethylation
  • Determinants of stage- and lineage-specific target selectivity unknown
  • Mechanism converting GFI1B from repressor to TCF activator undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0140110 transcription regulator activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005634 nucleus 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-4839726 Chromatin organization 2
Partners
CTNNB1EHMT2GATA1HDAC1HDAC2LSD1RCOR1SUV39H1
Complex memberships
LSD1-CoREST-HDAC1/2 (RCOR) corepressor complexbeta-catenin/GFI1B/LSD1 tripartite complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 GFI1B transcriptional repression is mediated through its SNAG domain, which recruits the corepressor CoREST, histone demethylase LSD1, and HDACs 1 and 2. Purification of GFI1B complexes identified these interacting proteins, and GFI1B further recruits these cofactors to the majority of target gene promoters in vivo. LSD1 depletion derepresses GFI1B targets accompanied by enhanced histone H3 lysine 4 methylation at respective promoters. Affinity purification of GFI1B complexes, Co-IP, ChIP, inhibition/knockdown of CoREST and LSD1 with lineage differentiation readouts Molecular cell High 17707228
2002 GFI1B is an essential transcriptional regulator required for erythroid and megakaryocytic lineage development in vivo. Gfi1b-null embryos fail to produce definitive enucleated erythrocytes and fetal liver contains erythroid and megakaryocytic precursors arrested in development, while myelopoiesis remains normal. Gene targeting (knockout mice), chimera analysis, histological and flow cytometric characterization Genes & development High 11825872
1998 GFI1B functions as a transcriptional repressor that directly binds a high-affinity site at -1518 to -1530 in the p21WAF1 promoter, repressing its expression. Forced expression of GFI1B (but not deletion mutants lacking the repressor domain) blocked IL-6-mediated induction of p21WAF1 and inhibited G1 arrest and differentiation of M1 myeloid cells. Reporter assays, promoter deletion/mutation, forced expression of GFI1B and deletion mutants, IL-6 differentiation assay Molecular and cellular biology High 9566867
2006 GFI1B localizes to pericentric heterochromatin (gamma-satellite sequences) and binds directly to the histone methyltransferases SUV39H1 and G9A. Elevated GFI1B levels correlate with increased histone H3 lysine 9 dimethylation at gamma-satellite and target gene promoter sites; GFI1B-deficient cells show decreased H3K9 trimethylation and loss of heterochromatic structures. ChIP-cloning protocol, immuno-FISH, Co-IP with SUV39H1 and G9A, analysis of GFI1B-deficient cells The EMBO journal High 16688220
2006 The SNAG domain is essential for all functions of GFI1B (and GFI1). Knock-in of GFI1B coding sequence into the GFI1 locus rescues pre-T-cell and neutrophil development (showing functional equivalence in hematopoiesis) but fails to rescue inner ear hair cell development, demonstrating cell-type-specific, domain-dependent functions. Knock-in mouse models (SNAG domain mutation; Gfi1-to-Gfi1b coding replacement), phenotypic analysis of hematopoiesis and inner ear EMBO reports High 16397623
2005 GFI1B directly auto-represses its own promoter and cross-represses the GFI1 promoter by binding to Gfi1/Gfi1b consensus sites in these promoters. Direct binding was demonstrated by gel-shift assays in vitro and by ChIP in vivo. Transgenic Gfi1b silences the endogenous Gfi1b locus in spleen but not bone marrow. Luciferase reporter assays, gel-shift (EMSA), ChIP, transgenic mice with vav-Gfi1b and GFP-tagged Gfi1 locus Nucleic acids research High 15718298
2004 GFI1B directly represses the GFI1 promoter through binding to conserved cis-element sequences. Both GFI1 and GFI1B mediate auto- and trans-regulation of the Gfi1 locus in primary mouse thymocytes and a human T-cell line, representing the first direct transcriptional target identified for these proteins. Reporter assays, EMSA, primary thymocyte experiments, human T-cell line transfection Nucleic acids research Medium 15131254
2005 GATA-1 (not GFI1B itself) directly binds to Gfi1-like sites in the GFI1B promoter to activate transcription; GFI1B suppresses GATA-1-mediated stimulation of its own promoter through protein-protein interaction with GATA-1, rather than by direct DNA binding to those sites. This constitutes a negative auto-regulatory feedback loop. Reporter assays, ChIP, Co-IP (protein interaction), EMSA Nucleic acids research Medium 16177182
2004 GATA-1 and NF-Y cooperate to activate erythroid-specific transcription of GFI1B. Both factors directly bind the GFI1B promoter (demonstrated by gel-shift and ChIP assays), and GATA-1-mediated transactivation requires NF-Y binding to the CCAAT site. Gel-shift (EMSA), ChIP, luciferase reporter assays, ectopic GATA-1 expression in non-erythroid cells Nucleic acids research Medium 15280509
2007 GFI1B is recruited to the Bcl-xL (Bcl-x) promoter through protein interaction with GATA-1, and elevated GFI1B suppresses GATA-1-induced Bcl-xL transcription. Transient GFI1B association with the promoter in early erythroid differentiation is followed by its release, allowing late Bcl-xL induction. GFI1B knockdown diminished imatinib-induced apoptosis while overexpression sensitized cells to death. ChIP, Co-IP (GFI1B-GATA-1 interaction), reporter assays, siRNA knockdown, overexpression in K562 cells Molecular and cellular biology Medium 17420275
2010 GFI1B controls erythrocyte and megakaryocyte development by regulating proliferation and differentiation of bipotent erythro-megakaryocytic progenitors. The type III TGF-beta receptor gene TGFBR3 is a direct transcriptional target of GFI1B. GFI1B knockdown results in altered TGF-beta signaling, increased Smad2 phosphorylation, and impaired Smad2/TIF1-gamma association, which normally directs erythroid differentiation. GFI1B knockdown in human progenitors, ChIP (TGFBR3 as direct target), phospho-Smad2 analysis, Smad2/TIF1-gamma co-IP Blood Medium 20124515
2013 GFI1B mutations that truncate the zinc finger DNA-binding domain act in a dominant-negative manner, inhibiting wild-type GFI1B transcriptional activity. The GFI1B Q287* mutant protein lacks functional DNA binding but retains the ability to interfere with wild-type GFI1B function, causing gray platelet syndrome. Functional reporter assays (dominant-negative activity), patient-derived mutation analysis, megakaryocyte characterization The New England journal of medicine Medium 24325358
2013 GFI1B frameshift mutation in the fifth zinc finger domain alters the transcriptional activity of the protein, resulting in reduced platelet alpha-granule content and aberrant expression of key platelet proteins, causing an autosomal dominant bleeding disorder with macrothrombocytopenia. Megakaryocytic cell line transfection with mutant construct, functional transcriptional assays, platelet protein expression analysis Journal of thrombosis and haemostasis : JTH Medium 23927492
2012 A short GFI1B isoform, p32 (generated by alternative splicing, lacking the first two zinc finger domains), associates more efficiently with the LSD1-CoREST repressor complex than the major p37 isoform. The SNAG domain KSKK motif recruits the repressor complex only when dimethylated on lysine 8; mutation of lysine 8 prevents GFI1B p32-induced erythroid development. Co-IP of p32/p37 with LSD1-CoREST, selective knockdown of p32, ectopic expression, SNAG domain mutagenesis (K8 mutation), erythroid differentiation assays Journal of cell science High 22399799
2013 GFI1B directly represses the oncogene Meis1 in erythroid cells by occupying its promoter together with cofactors LSD1 and CoREST/Rcor1. This repression is lineage-specific: it occurs in erythroid but not megakaryocyte cells. SNAG domain mutant and DNA-binding-deficient GFI1B mutants fail to repress meis1 promoter-driven reporters. Meis1 is significantly upregulated in LSD1-inhibited erythroid cells and in gfi1b-null fetal liver cells. ChIP, gene expression profiling, luciferase reporter assays with SNAG/DNA-binding mutants, LSD1 inhibition, gfi1b-null fetal liver analysis PloS one Medium 23308270
2016 The LSD1 inhibitor T-3775440 disrupts the interaction between LSD1 and GFI1B (via the SNAG domain), leading to transdifferentiation of erythroid/megakaryocytic leukemia cells into granulomonocytic-like cells. Knockdown of both LSD1 and GFI1B recapitulates this transdifferentiation and growth suppression, demonstrating the functional importance of the LSD1-GFI1B interaction axis. Co-IP (LSD1-GFI1B interaction disruption by inhibitor), siRNA knockdown of LSD1 and GFI1B, xenograft models, cell differentiation assays Molecular cancer therapeutics Medium 27903753
2017 LSD1 inhibitor T-3775440 disrupts the interaction between LSD1 and GFI1B (SNAG domain) in SCLC cells overexpressing GFI1B, inhibiting proliferation. In SCLC cells using INSM1 (another SNAG domain protein), the same inhibitor disrupts LSD1-INSM1 interaction and inhibits neuroendocrine gene expression. Co-IP (LSD1-GFI1B disruption), INSM1 silencing phenocopy experiments, cell proliferation assays, gene expression analysis Cancer research Medium 28667074
2019 GFI1B interacts most strongly with the LSD1-RCOR-HDAC complex in megakaryoblasts. The dominant-negative GFI1B Q287* mutant sequesters this complex, and chemical separation of GFI1B from LSD1 induces megakaryocyte abnormalities comparable to those seen in patients. iPSC-derived megakaryocytes with GFI1B Q287* phenocopy patient abnormalities. Co-IP/proteomics identifying LSD1-RCOR-HDAC as primary GFI1B complex, patient iPSC-derived megakaryocyte modeling, LSD1 inhibitor experiments, proteome studies Haematologica High 30655368
2019 GFI1B forms complexes with beta-catenin, Pontin52, CHD8, TLE3, and CtBP1 and regulates Wnt/beta-catenin-dependent gene expression. GFI1B can activate TCF-dependent transcription, and this requires interaction between GFI1B and LSD1, suggesting a tripartite beta-catenin/GFI1B/LSD1 complex. Treatment of GFI1B-deficient cells with Wnt3a restores normal cellularity and megakaryocyte spreading on integrin substrates. Co-IP (GFI1B with beta-catenin and co-factors), TCF reporter assays, Wnt3a rescue experiments, ChIP-seq (co-occupancy by GFI1B, beta-catenin, LSD1), integrin spreading assay Nature communications High 30894540
2014 GFI1B is required continuously in adult bone marrow at two distinct stages: an early bipotential progenitor stage in erythropoiesis and a promegakaryocyte stage (after polyploidization but before cytoplasmic maturation) in megakaryopoiesis. Genome-wide analyses revealed GFI1B predominantly represses a wide spectrum of megakaryocytic and erythroid genes. Inducible Cre-mediated conditional knockout in adult mice, flow cytometry, in vitro/in vivo differentiation assays, genome-wide ChIP and expression analysis The Journal of experimental medicine High 24711581
2012 GFI1 and GFI1B are direct targets of RUNX1 and act downstream of RUNX1 to trigger the endothelial-to-hematopoietic transition (EHT). GFI1/GFI1B can down-regulate endothelial markers and promote round cell morphology characteristic of EHT even in the absence of RUNX1. Blood progenitors in Gfi1/Gfi1b-deficient embryos maintain endothelial gene expression and fail to be released from the yolk sac. Gain-of-function rescue (GFI1/GFI1B expression in absence of RUNX1), loss-of-function in Gfi1/Gfi1b-deficient embryos, gene expression analysis of endothelial markers Blood Medium 22668850
2011 GFI1B represses Rag1 and Rag2 expression via a dual mechanism: direct binding to a site 5' of the B cell-specific Erag enhancer (causing epigenetic changes at the Rag locus), and indirect repression through transcriptional repression of the Rag transactivator FoxO1. GFI1B-deficient cell lines show increased Rag expression, double-strand breaks, abnormal V(D)J recombination, and cell cycle defects. cDNA library screen identifying GFI1B, GFI1B expression in cell lines and primary cells, ChIP (GFI1B binding to Erag enhancer), Gfi1b-deficient cell analysis, double-strand break and recombination assays The Journal of experimental medicine Medium 22201127
2017 GFI1B-deficient megakaryocytes fail to respond to integrin signaling and cannot spread or reorganize their cytoskeleton. GFI1B-null megakaryocytes show aberrant expression of actin and microtubule cytoskeleton components including dramatic reduction of alpha-tubulin. PAK inhibition completely rescues integrin responsiveness of GFI1B-null megakaryocytes, whereas FAK and ROCK inhibition only partially rescue; proplatelet formation defect is independent of integrin signaling. Megakaryocyte-specific conditional Gfi1b knockout, integrin spreading assays, cytoskeletal protein expression analysis, pharmacological inhibition of FAK/ROCK/PAK Haematologica Medium 28082345
2016 Patient-derived GFI1B mutations (including G272fsX274) abolish DNA binding to the consensus site (demonstrated by gel shift assay), fail to repress reporter gene expression, and exert dominant-negative effects over wild-type GFI1B. Transduction of fetal liver-derived megakaryocytes with mutant GFI1B produces abnormally large proplatelet tips reduced in number. Gel shift assay (EMSA), reporter assays, dominant-negative functional assays, transduction of fetal liver-derived megakaryocytes Journal of thrombosis and haemostasis : JTH Medium 27122003
2016 An alternative GFI1B splice variant preferentially promotes megakaryocyte differentiation and platelet production. A synonymous coding variant (rs150813342) suppresses formation of this isoform, reducing platelet count. CRISPR/Cas9 editing and targeted knockdown of this isoform in primary hematopoietic stem and progenitor cells confirmed its specific role in megakaryocyte differentiation. CRISPR/Cas9 genome editing, isoform-specific knockdown in primary HSPCs, whole-exome sequencing association study with functional follow-up American journal of human genetics Medium 27486782
2014 GFI1B is a regulator of embryonic globin gene expression. Conditional GFI1B deletion leads to upregulation of embryonic globin genes (Hba-x, Hbb-bh1, Hbb-y) without affecting Bcl11a expression, but with reduced Gata1 and near-complete loss of Sox6 expression, suggesting GFI1B regulates globin switching at least partially through Sox6. Conditional Gfi1b knockout mice (EpoR-Cre, Mx-Cre, Cre-ERT), global expression analysis of TER119+ fetal liver cells PloS one Medium 24800817
2015 GFI1B stringently represses Rgs18 expression in erythroid cells; during megakaryocytic differentiation, declining GFI1B levels allow robust Rgs18 induction. Rgs18 differentially impacts p38 MAPK and ERK1/2 signaling in the two lineages, altering the balance between the antagonistic transcription factors Fli1 and Klf1 to regulate erythro-megakaryocytic lineage choice. ChIP (GFI1B at Rgs18 promoter), Rgs18 overexpression/knockdown in erythroid and megakaryocytic cells, signaling pathway analysis (p38, ERK1/2), Fli1/Klf1 expression analysis Journal of cell science Medium 26567214
2018 LSD1 inhibitor NCD38 selectively disrupts the interaction of LSD1 with GFI1B but not with RUNX1, CoREST, HDAC1, or HDAC2 in erythroleukemia cells. This selective dissociation activates the ERG super-enhancer (which contains conserved GFI1B binding motifs and is occupied by GFI1B) by releasing LSD1 and CoREST but retaining GFI1B at the enhancer, inducing transdifferentiation. Proteome analysis identifying LSD1-associated proteins, Co-IP (selective disruption by NCD38), ChIP (GFI1B at ERG super-enhancer), lentiviral ERG overexpression, cell differentiation assays Oncotarget Medium 29765516
2024 GFI1B and LSD1 cooperate to repress myeloid traits during megakaryocyte differentiation. Patient-derived GFI1B Q287* variant uniquely fails to repress myeloid gene programs, causing a 4.5-fold decrease in megakaryocyte/myeloid ratio in iPSC-derived cells. Pharmacological inhibition of the GFI1B-LSD1 interaction with GSK-LSD1 activates myeloid genes in normal megakaryocytes similarly to GFI1B Q287*. Transcriptomic analysis of four patient GFI1B variants in MEG01 cells, single-cell RNA-seq of iPSC-derived megakaryocytes, pharmacological LSD1 inhibition Communications biology Medium 38548886
2022 GFI1B epigenetically regulates multiple fatty acid oxidation (FAO)-related genes. GFI1B deletion activates mitochondrial respiration and shifts metabolic dependence from glucose toward oxidative phosphorylation (OXPHOS) and fatty acid oxidation in hematopoietic stem cells and leukemia cells. Gfi1b conditional knockout in mice and leukemia models, metabolic flux analysis (mitochondrial respiration, FAO, OXPHOS), ChIP (epigenetic regulation of FAO genes), pharmacological inhibition of FAO/OXPHOS Leukemia Medium 35804097
2016 GFI1B D262N somatic mutation functionally antagonizes wild-type GFI1B transcriptional activity and promotes myelomonocytic over erythroid output. SPI1 (PU.1) is identified as a direct transcriptional target of GFI1B; GFI1B D262N elevates SPI1 expression, and SPI1 knockdown restores balanced lineage output from GFI1B D262N-expressing precursors. Functional transcriptional assays (mutant vs. wild-type), ChIP (GFI1B at SPI1 locus), SPI1 knockdown in GFI1B D262N-expressing precursors, lineage output assays Developmental biology Medium 26851695
2009 HMGB2 binds the GFI1B promoter in vivo and up-regulates GFI1B transcription by enhancing binding of Oct-1 and, to a lesser extent, GATA-1 and NF-Y. HMGB2 knockdown in hematopoietic progenitor cells decreases GFI1B expression and impairs erythroid differentiation. ChIP (HMGB2 at GFI1B promoter), reporter assays, HMGB2 knockdown in primary progenitors, erythroid differentiation assays Blood Medium 19965638
2010 Oct-1 and GATA-1 are identified as the main components of complexes binding to their respective sites in the GFI1B promoter. An Oct site mutation increases GFI1B RNA 4-5 fold in homozygous patient platelets, while a GATA motif mutation reduces promoter activity by 50% in vitro. EMSA demonstrated that binding is reduced by the mutations. EMSA with patient-derived promoter mutations, luciferase reporter assays, patient platelet RNA quantification Annals of hematology Medium 20143233
2024 GFI1B expression in uncommitted hemogenic endothelium (HE) cells is absent, yet ectopic GFI1B expression in uncommitted HE cells leads to downregulation of endothelial genes and upregulation of hematopoietic genes (GATA2, KIT, RUNX1, SPI1), inducing partial hematopoietic specification. LSD1 inhibition before EHT completely abolishes hematopoietic output, demonstrating temporally distinct roles of GFI1B and LSD1 during EHT. Patient iPSC with GFI1B Q287*, LSD1 pharmacological inhibition, ectopic GFI1B expression in uncommitted HE, scRNA-seq, gene expression analysis Haematologica Medium 38961746
2016 GFI1B directly represses Kindlin3 and Talin1 promoters (demonstrated by ChIP showing GFI1B and LSD1 enrichment). During megakaryocytic differentiation, declining GFI1B levels permit reciprocal upregulation of these cytoskeletal factors, which physically interact with integrin beta3/CD61 and positively regulate megakaryocytic differentiation. ChIP (GFI1B and LSD1 at Kindlin3/Talin1 promoters), knockdown/overexpression of Kindlin3 and Talin1, Co-IP (Kindlin3/Talin1 with integrin beta3), gfi1b mutant and LSD1 inhibited cell analysis PloS one Medium 27768697
2007 GFI1B is an E2A target gene in T lymphopoiesis. GFI1B represses Gata3 expression, and ectopic Gata3 promotes GFI1B expression, indicating an autoregulatory loop. GFI1B expression in primary T-lymphocyte progenitors is dependent on E2A, and excess GFI1B prevents outgrowth of T lymphocyte progenitors in vitro. E2A-deficient lymphoma cell experiments, GFI1B ectopic expression in progenitors, Gata3 expression analysis (as downstream target of GFI1B repression), in vitro progenitor outgrowth assay Blood Low 17272506

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1. Molecular cell 346 17707228
2002 The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages. Genes & development 200 11825872
2010 Gfi1 and Gfi1b: key regulators of hematopoiesis. Leukemia 158 20861919
2012 GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment. Blood 133 22668850
2013 A dominant-negative GFI1B mutation in the gray platelet syndrome. The New England journal of medicine 119 24325358
2002 Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis. Blood 109 12351384
1998 The Gfi-1B proto-oncoprotein represses p21WAF1 and inhibits myeloid cell differentiation. Molecular and cellular biology 107 9566867
2015 From cytopenia to leukemia: the role of Gfi1 and Gfi1b in blood formation. Blood 92 26447191
2016 A Novel LSD1 Inhibitor T-3775440 Disrupts GFI1B-Containing Complex Leading to Transdifferentiation and Impaired Growth of AML Cells. Molecular cancer therapeutics 88 27903753
2013 GFI1B mutation causes a bleeding disorder with abnormal platelet function. Journal of thrombosis and haemostasis : JTH 79 23927492
2017 LSD1 Inhibitor T-3775440 Inhibits SCLC Cell Proliferation by Disrupting LSD1 Interactions with SNAG Domain Proteins INSM1 and GFI1B. Cancer research 78 28667074
2004 Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells. Nucleic acids research 75 15131254
2010 Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage. Blood 74 20124515
2006 Gfi1 and Gfi1b act equivalently in haematopoiesis, but have distinct, non-overlapping functions in inner ear development. EMBO reports 72 16397623
2006 Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1. Blood 70 17095621
2005 Direct transcriptional repression of the genes encoding the zinc-finger proteins Gfi1b and Gfi1 by Gfi1b. Nucleic acids research 68 15718298
2004 Gfi-1B plays a critical role in terminal differentiation of normal and transformed erythroid progenitor cells. Blood 54 15507521
2006 Gfi1b alters histone methylation at target gene promoters and sites of gamma-satellite containing heterochromatin. The EMBO journal 53 16688220
2014 Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation. The Journal of experimental medicine 46 24711581
2009 Growth factor independent 1b (Gfi1b) and a new splice variant of Gfi1b are highly expressed in patients with acute and chronic leukemia. International journal of hematology 45 19360458
2005 GATA-1 mediates auto-regulation of Gfi-1B transcription in K562 cells. Nucleic acids research 44 16177182
2004 GATA-1 and NF-Y cooperate to mediate erythroid-specific transcription of Gfi-1B gene. Nucleic acids research 39 15280509
2016 Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and Reveals a Role for Alternative GFI1B Splice Variants in Human Hematopoiesis. American journal of human genetics 38 27486782
2007 Growth factor independent 1B (Gfi1b) is an E2A target gene that modulates Gata3 in T-cell lymphomas. Blood 38 17272506
2014 Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression. PloS one 36 24800817
2019 Gfi1b regulates the level of Wnt/β-catenin signaling in hematopoietic stem cells and megakaryocytes. Nature communications 35 30894540
2017 Transcription Factor GFI1B in Health and Disease. Frontiers in oncology 35 28401061
2007 GATA-1 and Gfi-1B interplay to regulate Bcl-xL transcription. Molecular and cellular biology 33 17420275
2012 A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain. Journal of cell science 32 22399799
2009 High-mobility group protein HMGB2 regulates human erythroid differentiation through trans-activation of GFI1B transcription. Blood 32 19965638
2020 Multifaceted Actions of GFI1 and GFI1B in Hematopoietic Stem Cell Self-Renewal and Lineage Commitment. Frontiers in genetics 31 33193732
2016 Functional characterization of a novel GFI1B mutation causing congenital macrothrombocytopenia. Journal of thrombosis and haemostasis : JTH 31 27122003
2006 Growth factor-independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate. British journal of haematology 31 17156408
2018 Selective dissociation between LSD1 and GFI1B by a LSD1 inhibitor NCD38 induces the activation of ERG super-enhancer in erythroleukemia cells. Oncotarget 27 29765516
2017 In Vivo Generation of Engraftable Murine Hematopoietic Stem Cells by Gfi1b, c-Fos, and Gata2 Overexpression within Teratoma. Stem cell reports 27 28943250
2016 Combined alpha-delta platelet storage pool deficiency is associated with mutations in GFI1B. Molecular genetics and metabolism 27 28041820
2013 Differential transcriptional regulation of meis1 by Gfi1b and its co-factors LSD1 and CoREST. PloS one 26 23308270
2011 Gfi1b negatively regulates Rag expression directly and via the repression of FoxO1. The Journal of experimental medicine 26 22201127
2019 Molecular mechanisms of bleeding disorderassociated GFI1BQ287* mutation and its affected pathways in megakaryocytes and platelets. Haematologica 24 30655368
2009 GFI1B controls its own expression binding to multiple sites. Haematologica 24 19773260
2017 Gfi1b controls integrin signaling-dependent cytoskeleton dynamics and organization in megakaryocytes. Haematologica 23 28082345
2022 GFI1B acts as a metabolic regulator in hematopoiesis and acute myeloid leukemia. Leukemia 22 35804097
2013 Additive antileukemia effects by GFI1B- and BCR-ABL-specific siRNA in advanced phase chronic myeloid leukemic cells. Cancer gene therapy 22 23788109
2009 Gfi-1B promoter remains associated with active chromatin marks throughout erythroid differentiation of human primary progenitor cells. Stem cells (Dayton, Ohio) 22 19522008
2018 Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome. Haematologica 19 29326122
2016 A somatic mutation of GFI1B identified in leukemia alters cell fate via a SPI1 (PU.1) centered genetic regulatory network. Developmental biology 18 26851695
2020 Human yolk sac-like haematopoiesis generates RUNX1-, GFI1- and/or GFI1B-dependent blood and SOX17-positive endothelium. Development (Cambridge, England) 17 33028609
2021 The transcription factors GFI1 and GFI1B as modulators of the innate and acquired immune response. Advances in immunology 15 33993920
2012 Valproic acid triggers erythro/megakaryocyte lineage decision through induction of GFI1B and MLLT3 expression. Experimental hematology 12 22885124
2007 Gene profiling of growth factor independence 1B gene (Gfi-1B) in leukemic cells. International journal of hematology 11 18224412
2023 Gata2-regulated Gfi1b expression controls endothelial programming during endothelial-to-hematopoietic transition. Blood advances 10 36649572
2019 Macrothrombocytopenia associated with a rare GFI1B missense variant confounding the presentation of immune thrombocytopenia. Pediatric blood & cancer 10 31207059
2018 Gfi1aa and Gfi1b set the pace for primitive erythroblast differentiation from hemangioblasts in the zebrafish embryo. Blood advances 10 30309860
2015 Reciprocal regulation of alternative lineages by Rgs18 and its transcriptional repressor Gfi1b. Journal of cell science 9 26567214
2013 GFI1B, EVI5, MYB--additional genes that cooperate with the human BCL6 gene to promote the development of lymphomas. Blood cells, molecules & diseases 9 23910958
2020 Dominant negative Gfi1b mutations cause moderate thrombocytopenia and an impaired stress thrombopoiesis associated with mild erythropoietic abnormalities in mice. Haematologica 8 33054086
2010 Human promoter mutations unveil Oct-1 and GATA-1 opposite action on Gfi1b regulation. Annals of hematology 8 20143233
2024 GFI1B specifies developmental potential of innate lymphoid cell progenitors in the lungs. Science immunology 7 38820141
2014 Associations between polymorphisms of the GFI1B gene and growth traits of indigenous Chinese goats. Genetics and molecular research : GMR 7 24615051
2013 Gfi1 and gfi1b repress rag transcription in plasmacytoid dendritic cells in vitro. PloS one 6 24086657
2023 Novel EWSR1::GFI1B gene fusion in angiofibroma of soft tissue. Histopathology 5 37680034
2020 A novel homozygous GFI1B variant in 2 sisters with thrombocytopenia and severe bleeding tendency. Platelets 5 32633597
2024 GFI1B and LSD1 repress myeloid traits during megakaryocyte differentiation. Communications biology 4 38548886
2024 LSD1/KDM1A and GFI1B repress endothelial fate and induce hematopoietic fate in induced pluripotent stem cell-derived hemogenic endothelium. Haematologica 4 38961746
2023 Aggregates of nonmuscular myosin IIA in erythrocytes associate with GATA1- and GFI1B-related thrombocytopenia. Journal of thrombosis and haemostasis : JTH 4 38103735
2017 Generation and characterization of a human iPSC line SANi005-A containing the gray platelet associated heterozygous mutation p.Q287* in GFI1B. Stem cell research 4 29055225
2016 Cooperative Stimulation of Megakaryocytic Differentiation by Gfi1b Gene Targets Kindlin3 and Talin1. PloS one 4 27768697
2022 Dysregulation of oncogenic factors by GFI1B p32: investigation of a novel GFI1B germline mutation. Haematologica 3 33472357
2022 Fuchs Endothelial Corneal Dystrophy associated risk variant, rs3768617 in LAMC1 shows allele specific binding of GFI1B. Gene 3 35031421
2009 Altered functional balance of Gfi-1 and Gfi-1b as an alternative cause of reticular dysgenesis? Medical hypotheses 3 19896777
2023 An oligogenic case of severe neonatal thrombocytopenia and a purportedly benign variant in GFI1B requiring reinterpretation. Platelets 2 37577973
2025 A Novel Homozygous GFI1B Mutation in Siblings With Thrombocytopenia and Bleeding Tendency. Clinical case reports 1 41040832
2014 Regulation of histamine synthesis and tryptase expression through transcription factors, growth factor independent 1 (Gfi1) and Gfi1b, in murine cultured mast cells. Biological & pharmaceutical bulletin 1 24389484
2026 GFI1B mutations define an emerging form of inherited thrombocytopenia: insights from a case report and literature review. Annals of hematology 0 41766040
2021 Characterization of a genomic region 8 kb downstream of GFI1B associated with myeloproliferative neoplasms. Biochimica et biophysica acta. Molecular basis of disease 0 34450246
2013 cDNA cloning and analysis of polymorphism of GFI1B gene in GuiZhou white goat. Genetika 0 25470932

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