Affinage

MEIS2

Homeobox protein Meis2 · UniProt O14770

Length
477 aa
Mass
51.8 kDa
Annotated
2026-06-10
83 papers in source corpus 29 papers cited in narrative 29 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

MEIS2 is a TALE-class homeodomain transcription factor that assembles context-dependent regulatory complexes to control cell-fate specification across multiple developmental programs (PMID:9710595, PMID:24284204). It functions principally as a transcriptional activator whose C-terminal activation domain is autoinhibited by its homothorax (Hth) domain, an autoinhibition partially relieved by PBX1 binding, while splice variants disrupting the Hth domain or homeodomain can derepress activation or act as dominant negatives (PMID:10764806, PMID:20553494). Through DNA binding and partner-dependent complexes with PBX1/PDX1, Pax6/Dlx2, Otx2, Pax3/7, Klf4, and SHOX2, MEIS2 directs distinct transcriptional outputs—switching PDX1 activity in pancreatic acinar cells (PMID:9710595), relieving Otx2 repression by competing with Groucho co-repressors during tectal development (PMID:19736326), activating doublecortin and tyrosine hydroxylase in olfactory-bulb neurogenesis (PMID:24284204), and binding Zfp503 and Six3 promoters to specify striatal medium-spiny-neuron identity (PMID:35156680). In limb development MEIS2 establishes proximal identity that antagonizes distal outgrowth and is spatially restricted by PRC1/RING1-mediated epigenetic repression in the distal bud, a repression axis genetically required for proximal-distal patterning (PMID:10619030, PMID:26674308, PMID:30190278); its midbrain activation depends on a tissue-specific enhancer-promoter topological switch controlled by RING1 (PMID:24374176). MEIS2 is essential for cranial and cardiac neural crest development, palatal and craniofacial skeletogenesis via direct regulation of osteogenic genes and SHOX2, inner ear morphogenesis, and end-organ innervation by cutaneous mechanoreceptors (PMID:26545946, PMID:32169905, PMID:32616504, PMID:34124068, PMID:38386003). Its abundance and localization are tuned post-translationally: arginine methylation impairs CRM1-mediated nuclear export to promote neuronal differentiation (PMID:29641989), calpain-2 cleaves MEIS2 unless protected by phosphorylation or PBX1 dimerization (PMID:38305737), O-GlcNAcylation at Ser237 blocks ubiquitination to stabilize the protein (PMID:41936590), and the CRL4-cereblon E3 ligase targets MEIS2 in a manner modulated by IMiDs (PMID:30975979). In disease contexts MEIS2 promotes neuroblastoma mitotic progression through FOXM1 (PMID:25210800) and collaborates with AML1-ETO leukemogenesis (PMID:27346355).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1998 High

    Established that MEIS2 is not a solitary DNA-binding factor but a combinatorial partner that reprograms the activity of a co-bound homeodomain protein, defining its mechanistic mode of action.

    Evidence Co-IP, EMSA, and reporter assays on the pancreatic elastase I enhancer in acinar versus beta-cell lines

    PMID:9710595

    Open questions at the time
    • Did not define MEIS2's intrinsic activation/repression contribution separate from PDX1/PBX1
    • Restricted to pancreatic acinar context
  2. 1999 High

    Placed MEIS2 in a developmental patterning role, showing it confers proximal limb identity and antagonizes distal outgrowth downstream of BMP and Hox cues.

    Evidence Retroviral misexpression in chick limb buds with distal-marker readouts and BMP/Hoxd epistasis

    PMID:10619030

    Open questions at the time
    • Gain-of-function only; endogenous requirement not tested here
    • Direct target genes in limb not identified
  3. 2000 High

    Defined MEIS2 as a direct, sequence-specific transcriptional activator and revealed that splice variants and competitor TGIF modulate this activity, including a dominant-negative isoform.

    Evidence EMSA, luciferase reporters across isoforms, and dominant-negative overexpression on the dopamine D1A receptor promoter

    PMID:10764806

    Open questions at the time
    • Physiological roles of individual isoforms not established
    • TGIF competition not validated in vivo
  4. 2010 High

    Resolved the molecular basis of MEIS2 transcriptional control by showing the Hth domain autoinhibits the activation domain and PBX1 binding relieves it.

    Evidence Domain deletion/fusion constructs, Gal4 activation assays, and Co-IP for Pbx1 interaction

    PMID:20553494

    Open questions at the time
    • Structural mechanism of autoinhibition not solved
    • Whether all partner complexes relieve autoinhibition similarly unknown
  5. 2009 High

    Showed MEIS2 can act by relieving repression—competing with a Groucho co-repressor for Otx2—broadening its mechanistic repertoire beyond direct activation.

    Evidence Reciprocal Co-IP, Otx2-dependent reporter, and in ovo electroporation in chick mesencephalon

    PMID:19736326

    Open questions at the time
    • Direct target genes downstream of Otx2 derepression not mapped
    • Single developmental context
  6. 2013 High

    Identified MEIS2 as a cell-autonomous driver of adult SVZ neurogenesis and named its first direct neuronal targets, linking the factor to dopaminergic neuron generation.

    Evidence Co-IP for a Meis2-Pax6-Dlx2 complex, ChIP for doublecortin/TH targets, and retroviral loss-of-function in vivo

    PMID:24284204

    Open questions at the time
    • Genome-wide target set not defined here
    • Stoichiometry of the tripartite complex unknown
  7. 2013 High

    Revealed how MEIS2 itself is transcriptionally controlled by a RING1-dependent enhancer-promoter topological switch during midbrain activation.

    Evidence ChIP, 3C chromatin conformation capture, and Ring1B conditional knockout mouse

    PMID:24374176

    Open questions at the time
    • Factors triggering RBS dissociation unknown
    • Generality of the topological switch to other tissues untested
  8. 2015 High

    Established a genetic PRC1-MEIS2 repression axis required for proximal-distal limb specification, with RA-related signals competing to polarize Meis2 expression.

    Evidence Ring1A/B and PCGF3/5 conditional knockouts, Meis2 compound-mutant rescue, ChIP, and RA pathway epistasis

    PMID:26674308 PMID:30190278

    Open questions at the time
    • Direct PRC1 recruitment mechanism at the Meis2 locus incompletely defined
    • Quantitative threshold of Meis2 derepression needed for distal defects unclear
  9. 2015 High

    Demonstrated an essential requirement for MEIS2 in neural crest derivatives, with loss causing craniofacial, cardiac outflow, and cranial nerve defects and systemic loss being embryonic-lethal.

    Evidence AP2α-IRES-Cre and systemic Meis2 knockout mice with histology and immunofluorescence

    PMID:26545946

    Open questions at the time
    • Direct neural-crest target genes not identified in this study
    • Cause of embryonic lethality/hemorrhage not mechanistically resolved
  10. 2020 High

    Provided genome-wide direct target maps in palatal neural crest, identifying SHOX2 as both partner and target and tying MEIS2 to osteogenic gene regulation and Shh-dependent arch patterning.

    Evidence ChIP-seq, ATAC-seq, RNA-seq, Co-IP, and Wnt1-Cre conditional knockouts with palatal/arch phenotypes

    PMID:32169905 PMID:32616504

    Open questions at the time
    • Whether MEIS2-SHOX2 co-occupancy is direct cooperative binding at all sites unresolved
    • Link between Shh loss and downstream ossification incompletely mapped
  11. 2022 High

    Defined MEIS2's role in striatal MSN fate, showing it acts downstream of Dlx1/2 via enhancer hs599 and directly binds Zfp503 and Six3 to specify D1/D2 neuron identity.

    Evidence Meis2 conditional knockout, ChIP for direct promoter binding, and Dlx1/2 epistasis

    PMID:35156680

    Open questions at the time
    • How a single factor selects D1 versus D2 programs not resolved
    • Cofactors at Zfp503/Six3 promoters not defined
  12. 2021 High

    Extended MEIS2's organogenesis roles to inner ear formation and cochlear duct coiling with tissue-specific direct candidate targets.

    Evidence Hindbrain- and inner-ear-specific conditional knockouts, RNA-seq, and ChIP-seq in an otic cell line

    PMID:34124068

    Open questions at the time
    • Functional validation of individual otic targets pending
    • Cell-autonomous versus hindbrain-relayed requirement partially separated
  13. 2024 High

    Showed MEIS2 governs cutaneous mechanoreceptor maturation, controlling end-organ innervation, electrophysiology, and touch behavior without affecting neuron survival.

    Evidence LTMR-specific conditional knockouts with electrophysiology, behavior, morphology, and RNA-seq

    PMID:38386003

    Open questions at the time
    • Direct transcriptional targets driving innervation morphology not identified
    • Target-derived signal controlling Meis2 expression unknown
  14. 2018 High

    Identified arginine methylation as a post-translational switch that retains MEIS2 in the nucleus by blocking CRM1 export, coupling the PTM to neuronal differentiation.

    Evidence Site-directed methylation mutagenesis, Co-IP of CRM1/PBX1, and subcellular fractionation in SVZ progenitors

    PMID:29641989

    Open questions at the time
    • Methyltransferase responsible not identified
    • Whether methylation alters DNA binding or only localization unclear
  15. 2024 High

    Established calpain-2 proteolysis as a determinant of MEIS2 full-length stability during neurogenesis, with phosphorylation or PBX1 dimerization protecting against cleavage.

    Evidence Reconstituted in vitro cleavage assay, phospho-site mutagenesis, Co-IP, and calpain-2 manipulation in V-SVZ progenitors

    PMID:38305737

    Open questions at the time
    • Cleavage products' fate and any function not characterized
    • Kinase mediating protective phosphorylation not identified
  16. 2026 Medium

    Showed O-GlcNAcylation at Ser237 stabilizes MEIS2 by blocking ubiquitination, linking nutrient-sensing glycosylation to palatal osteogenic homeostasis.

    Evidence O-GlcNAc-IP, Ser237 mutagenesis, ubiquitination assays, and zebrafish OGT loss-of-function

    PMID:41936590

    Open questions at the time
    • E3 ligase opposing this PTM in palate not identified
    • Crosstalk with calpain and CRBN pathways untested
  17. 2019 Medium

    Identified MEIS2 as a cereblon (CRL4-CRBN) substrate whose IMiD-blockable binding links it to therapeutic E3-ligase modulation and Cyclin E regulation in myeloma.

    Evidence Crystal-structure substrate identification, RNAi knockdown, and viability/apoptosis assays

    PMID:30975979

    Open questions at the time
    • In vivo physiological role of CRBN-mediated MEIS2 turnover unknown
    • Degron determinants on MEIS2 not fully mapped
  18. 2014 High

    Connected MEIS2 to mitotic gene control in cancer, showing it activates the MuvB-BMYB-FOXM1 program with FOXM1 as a direct target required for neuroblastoma survival.

    Evidence siRNA/overexpression with M-phase readouts, ChIP for FOXM1, and rescue experiments

    PMID:25210800

    Open questions at the time
    • Whether the FOXM1 axis operates in normal proliferating cells unclear
    • Upstream control of MEIS2 in neuroblastoma not defined
  19. 2016 Medium

    Showed MEIS2 binds the AML1-ETO Runt domain and collaborates in leukemogenesis by relieving AML1-ETO repressive DNA binding and inducing YES1.

    Evidence Co-IP of the Runt-domain interaction, shRNA knockdown in AML lines, and a murine leukemia model

    PMID:27346355

    Open questions at the time
    • Direct MEIS2 binding sites genome-wide in AML not mapped
    • Single lab; reciprocal validation limited
  20. 2025 Medium

    Extended the MEIS2-CRBN axis to show CDK4/6 inhibition accelerates IMiD-driven MEIS2 displacement and destabilization, enhancing IKZF degradation and modulating BCMA in myeloma.

    Evidence Biochemical displacement and ubiquitination assays with ex vivo primary myeloma cells (preprint)

    PMID:41279046

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Mechanism by which CDK4/6 inhibition raises CRBN unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How alternative splicing generates functionally distinct MEIS2 isoforms with different transcriptional targets across cell-state transitions remains incompletely defined.
  • Full target repertoires of distinct isoforms unmapped
  • Whether PTM regulation differs between isoforms unknown
  • In vivo phenotypic consequences of isoform balance largely untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005654 nucleoplasm 3 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-4839726 Chromatin organization 3
Partners
CRM1DLX2KLF4OTX2PAX6PBX1PDX1SHOX2
Complex memberships
CRL4-cereblon (CRBN) E3 ubiquitin ligase (as substrate)MEIS2-PBX1-PDX1 trimeric complexMEIS2-Pax6-Dlx2 complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MEIS2 (MRG1) forms a trimeric complex with PBX1b and PDX1 on the B element of the pancreatic elastase I gene enhancer in acinar cells, switching PDX1 transcriptional activity from beta-cell-type activation to acinar-cell-type activity dependent on other enhancer elements; beta-cell lines lack PBX1b and MRG1/MEIS2, preventing trimeric complex formation. Co-immunoprecipitation, electrophoretic mobility shift assay, transcriptional reporter assays in acinar and beta-cell lines, B element mutagenesis Molecular and cellular biology High 9710595
1999 Ectopic Meis2 expression in the chick limb bud severely disrupts distal limb outgrowth and represses distal genes; Meis2 is normally restricted to proximal regions by BMPs and Hoxd genes, establishing a proximal identity that antagonizes distal outgrowth. Retroviral misexpression in chick limb buds, in situ hybridization for distal markers, epistasis with BMP and Hoxd gene manipulations Molecular cell High 10619030
2000 Meis2 isoforms (a-d) bind the ACT activator sequence of the dopamine D1A receptor gene promoter and activate transcription; TGIF competes with Meis2 for binding to this site and represses Meis2-induced activation. Splice variant Meis2e, with a truncated homeodomain, cannot bind DNA or activate transcription but acts as a dominant-negative inhibitor of Meis2d-induced transcription. EMSA (DNA binding assay), luciferase transcriptional reporter assays in multiple cell types, dominant-negative overexpression The Journal of biological chemistry High 10764806
2009 Meis2 physically interacts with Otx2 and competes with the Groucho co-repressor Tle4 (Grg4) for binding to Otx2, thereby relieving Otx2 transcriptional repression and restoring its activator function during tectal development in chick. Co-immunoprecipitation, Otx2-dependent reporter assay, in ovo electroporation gain- and loss-of-function in chick mesencephalic vesicle Development (Cambridge, England) High 19736326
2010 The homothorax (Hth) domain of Meis2 autoinhibits its C-terminal transcriptional activation domain; this autoinhibition is partially relieved by Pbx1 binding to the Hth domain. A splice variant equivalent to Meis3.2 that disrupts the Hth domain derepresses the activation domain and weakens Pbx1 interaction. Transcriptional reporter assays, domain deletion and fusion constructs, Gal4-based activation domain assays, co-immunoprecipitation for Pbx1 interaction The FEBS journal High 20553494
2011 Meis2 interacts with Klf4 and Pbx1 to cooperatively activate transcription of p15(Ink4a) and E-cadherin; Meis2d transcriptional activation domain is required for this cooperative activation, and reducing endogenous Meis2 or Pbx1 decreases p15 expression and increases S-phase entry. Co-immunoprecipitation, luciferase reporter assays, ChIP, siRNA knockdown of endogenous Meis2/Pbx1 with cell cycle readout, promoter mutagenesis Molecular and cellular biology High 21746878
2012 Meis2 physically interacts with Pax3 and Pax7 in the tectal anlage; Meis2 acts downstream of Pax3/Pax7 and requires balanced expression of both proteins, as demonstrated by in ovo electroporation in chick mesencephalic vesicle. Co-immunoprecipitation, in ovo electroporation gain- and loss-of-function, in situ hybridization BMC developmental biology Medium 22390724
2013 Meis2 forms a biochemical complex with Pax6 and Dlx2 in the olfactory bulb neurogenic system; ChIP identified doublecortin and tyrosine hydroxylase as direct Meis2 target genes in newly generated neurons; Meis2 activity is cell-autonomously required for neuronal fate acquisition by SVZ progenitors and for generation of dopaminergic periglomerular neurons. Co-immunoprecipitation (Meis2-Pax6-Dlx2 complex), chromatin immunoprecipitation (doublecortin and TH as direct targets), retroviral dominant-negative and siRNA knockdown in vivo and in vitro Development (Cambridge, England) High 24284204
2013 Polycomb RING1B binds the Meis2 promoter and a 3'-end RING1B-binding site (RBS) to repress Meis2; during early midbrain development, a midbrain-specific enhancer (MBE) forms a tripartite interaction with the promoter and RBS in a RING1-dependent manner, and subsequent dissociation of the RBS allows promoter-MBE engagement to activate Meis2 expression. ChIP, 3C/chromatin conformation capture, Ring1B conditional knockout mouse, in situ hybridization Developmental cell High 24374176
2014 MEIS2 is required for neuroblastoma cell survival and M-phase progression; MEIS2 functions as a transcriptional activator of the MuvB-BMYB-FOXM1 complex, and FOXM1 is a direct transcriptional target of MEIS2 required for MEIS2-induced upregulation of mitotic genes. siRNA knockdown, ectopic overexpression with proliferation/tumorigenicity assays, gene expression profiling, ChIP (FOXM1 as direct target), rescue experiments Cell death & disease High 25210800
2015 RING1A and RING1B (PRC1 components) are required for repression of Meis2 (and Meis1) in the distal forelimb bud; additional deletion of Meis2 in Ring1A/B-deficient mice partially restores distal gene expression and limb formation, establishing a RING1-MEIS2 repression axis critical for proximal-distal specification. Conditional double knockout mice (Ring1A/B), Meis2 compound knockout rescue experiment, in situ hybridization, RING1B ChIP Development (Cambridge, England) High 26674308
2015 Conditional inactivation of Meis2 in neural crest cells (AP2α-IRES-Cre) causes defects in craniofacial skeleton (cranial bones and cartilages), persistent truncus arteriosus, and cranial nerve abnormalities; systemic Meis2 knockout results in embryonic lethality by E14 with hemorrhaging. Conditional knockout mouse (AP2α-IRES-Cre; Meis2fl/fl), systemic knockout mouse, histology, immunofluorescence BMC developmental biology High 26545946
2016 MEIS2 binds directly to the Runt domain of AML1-ETO; high MEIS2 expression impairs repressive DNA binding of AML1-ETO and induces increased expression of proto-oncogene YES1; MEIS2 collaborates with AML1-ETO to induce AML in mice. Co-immunoprecipitation (MEIS2-AML1-ETO Runt domain interaction), shRNA knockdown in AML cell lines, murine leukemia model, gene expression analysis Cell reports Medium 27346355
2016 In castration-resistant prostate cancer, MEIS2 is repressed by miR-196b-3p as part of a constitutively activated feedforward circuit composed of IκBα/NF-κB(p65), miR-196b-3p, Meis2, and PPP3CC that drives stem cell transcription factor expression and tumorigenicity. miRNA target validation, luciferase reporter assay, siRNA/shRNA knockdown of circuit components, in vivo tumorigenicity assays, NF-κB reporter assays Molecular cell Medium 28041912
2018 MEIS2 nuclear accumulation in adult SVZ-derived progenitor cells is controlled by arginine methylation: methylation of a conserved arginine on MEIS2 (near CRM1 and PBX1 binding sites) impairs interaction with the nuclear export receptor CRM1 without affecting PBX1 dimerization, thereby allowing MEIS2 nuclear accumulation required for neuronal differentiation. Co-immunoprecipitation (CRM1 and PBX1 interactions), arginine methylation site mutagenesis, subcellular fractionation, retroviral constructs in SVZ progenitors, EGFR signaling manipulation Stem cell reports High 29641989
2018 Variant PRC1 incorporating PCGF3 and PCGF5 represses Meis2 in the distal forelimb bud by antagonizing retinoic acid-related signals; PcG factors and RA-related signals compete to polarize Meis2 expression along the proximal-distal axis. Conditional knockout mice (PCGF3/5), ChIP, mathematical modeling, RA pathway manipulation, in situ hybridization Development (Cambridge, England) High 30190278
2018 MEIS2 regulates the endothelial-to-hematopoietic transition (EHT) during hematopoietic differentiation of human embryonic stem cells; TAL1 acts as a downstream gene mediating MEIS2 function during early hematopoiesis, as deletion of MEIS2 suppresses TAL1 expression and impairs hemogenic endothelial specification. CRISPR/Cas9 MEIS2 deletion in hESCs, hematopoietic differentiation assays, whole-genome gene profiling, TAL1 rescue experiments Stem cell research & therapy Medium 30526668
2019 PTBP1 upregulates the MEIS2-L splice variant to promote bladder cancer cell migration and invasion; overexpression of MEIS2-L rescues the reduced migration and invasion caused by PTBP1 knockdown, and MEIS2-L is associated with increased MMP9 expression. siRNA knockdown of PTBP1, alternative splicing analysis, MEIS2-L overexpression rescue experiments, invasion and migration assays, in vivo lymph node metastasis model Cancer letters Medium 30742945
2019 MEIS2 is a substrate of the CRL4-cereblon (CRBN) E3-ubiquitin ligase complex; MEIS2 was identified as a cereblon substrate by crystal structure and biochemical screen, and IMiDs can block MEIS2 from binding CRBN, facilitating CRL4CRBN-IMiD E3 ubiquitin ligase activity. MEIS2 regulates Cyclin E/CCNE1 expression and modulates IMiD activity in multiple myeloma cells. Crystal structure (biochemical identification as CRBN substrate), RNA interference knockdown, cell viability and apoptosis assays, BET inhibitor modulation of MEIS2 expression Cell death & disease Medium 30975979
2019 siRNA-mediated simultaneous knockdown of Rb1 and Meis2 in adult cardiomyocytes promotes cell cycle reentry, increases cardiomyocyte number, decreases cell size, increases mononucleated cardiomyocytes in vitro, and in vivo reduces infarct size and improves cardiac function post-myocardial infarction, implicating Meis2 as a senescence-associated cell cycle inhibitor in adult cardiomyocytes. siRNA knockdown in adult rat and human iPSC-derived cardiomyocytes, EdU/PH3/Ki67/Aurora B immunostaining, hydrogel siRNA delivery post-MI in vivo, echocardiography Journal of the American Heart Association Medium 31315484
2020 MEIS2 directly regulates key osteogenic genes in palatal neural crest cells as determined by ChIP-seq; MEIS2 physically interacts with SHOX2, and SHOX2 is a direct downstream target of MEIS2, with genome-wide MEIS2-SHOX2 co-occupancy identified by comparative ChIP-seq. Wnt1-Cre-mediated Meis2 inactivation results in secondary palate cleft and absence of palatal bones. ChIP-seq, RNA-seq, ATAC-seq, Wnt1-Cre conditional knockout mouse, Co-immunoprecipitation (MEIS2-SHOX2 physical interaction), de novo motif analysis The Journal of biological chemistry High 32169905
2020 Meis2 inactivation in cranial neural crest cells results in loss of Sonic hedgehog signaling in oropharyngeal epithelium and impaired patterning of the first pharyngeal arch (PA1) along lateral-medial and oral-aboral axes, leading to hypoplastic tongue and ectopic mandibular ossification. Conditional knockout mouse (Wnt1-Cre;Meis2fl/fl), in situ hybridization for Shh pathway components, expression analysis of Hand1/2, Dlx5, Barx1, Gsc Biology open High 32616504
2021 Meis2 is required for inner ear formation: hindbrain-specific Meis2 expression is essential for otic vesicle formation, and inner-ear-specific Meis2 knockout leads to aberrant cochlear duct coiling. ChIP-seq of an otic cell line combined with transcriptomics identified direct candidate Meis2 target genes in cochlear morphogenesis. Tissue-specific conditional knockout mice (hindbrain and inner-ear specific Cre lines), RNA-seq of Meis2 mutant otic vesicles, ChIP-seq in otic cell line Frontiers in cell and developmental biology High 34124068
2022 Dlx1/2 drives Meis2 expression in the lateral ganglionic eminence (LGE) subventricular zone through enhancer hs599; Meis2 directly binds the Zfp503 and Six3 promoters and is required for their expression to specify D1 and D2 medium-sized spiny neurons (MSNs) respectively; Meis2 deletion causes a large reduction in striatal MSNs due to a block in differentiation. Conditional knockout mouse (Meis2fl/fl), ChIP (direct binding to Zfp503 and Six3 promoters), in situ hybridization, Dlx1/2 knockout epistasis, enhancer hs599 characterization Development (Cambridge, England) High 35156680
2024 Meis2 is a direct substrate of the intracellular protease calpain-2 (CAPN2/CAPNS1 complex); phosphorylation at conserved serine/threonine residues or dimerization with PBX1 reduces MEIS2 sensitivity to calpain-2 cleavage. Calpain-2 activity is high in SVZ stem/progenitor cells and declines during neuronal differentiation, inversely correlated with MEIS2 full-length stability; blocking calpain-2 or expressing cleavage-insensitive MEIS2 increases neuron production. In vitro calpain-2 cleavage assay (reconstituted), phosphorylation site mutagenesis, Co-IP (PBX1 dimerization), immunofluorescence in adult V-SVZ, calpain-2 overexpression/inhibition in progenitor cells, cleavage-insensitive MEIS2 overexpression Journal of cell science High 38305737
2024 Meis2 is specifically expressed in cutaneous low-threshold mechanoreceptors (LTMRs) in mice, dependent on target-derived signals; LTMRs lacking Meis2 survive and are normally specified but show markedly impaired end-organ innervation morphology, altered electrophysiological properties, and an altered transcriptome, resulting in impaired sensory-evoked behavioral responses. Conditional knockout mouse (LTMR-specific Cre lines), in vivo electrophysiology, behavioral touch response assays, immunofluorescence for end-organ morphology, RNA-seq eLife High 38386003
2026 OGT-mediated O-GlcNAcylation of MEIS2 at serine 237 maintains MEIS2 protein stability by inhibiting its ubiquitination; reduced O-GlcNAcylation leads to increased MEIS2 ubiquitination and degradation, impairing osteogenic homeostasis in palatal development. O-GlcNAc-IP, site-directed mutagenesis (Ser237), ubiquitination assay, zebrafish OGT loss-of-function model, Western blot for protein stability, cleft palate mouse model International journal of oral science Medium 41936590
2025 CDK4/6 inhibition accelerates displacement of MEIS2 from CRBN by IMiDs and destabilizes MEIS2 protein while increasing CRBN, enhancing CRL4CRBN-mediated ubiquitination of IKZF3 and IKZF1 for degradation; MEIS2 also promotes BCMA expression and antagonizes IMiD/CELMoD-mediated BCMA repression in myeloma cells. Biochemical displacement assay (MEIS2-CRBN), protein stability assays, ubiquitination assays for IKZF1/3, BCMA expression analysis, ex vivo primary bone marrow myeloma cell experiments with CDK4/6 inhibitors and IMiDs bioRxivpreprint Medium 41279046
2025 In developing neocortex, Rbfox proteins induce a progenitor-to-neuron isoform switch in Meis2; the progenitor isoform of Meis2 promotes Tgfb3 transcription, while the neuron isoform promotes neuronal differentiation, demonstrating that alternative splicing of Meis2 generates functionally distinct isoforms with different transcriptional targets. Cell-type-specific RNA-seq, Rbfox1/2/3 conditional triple knockout in neocortex, Meis2 isoform overexpression with Tgfb3 promoter reporter assay, neuronal migration assay bioRxivpreprint Medium bio_10.1101_2024.09.09.612108

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin. Molecular cell 251 10619030
2010 miR-204 is required for lens and retinal development via Meis2 targeting. Proceedings of the National Academy of Sciences of the United States of America 157 20713703
1998 An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2). Molecular and cellular biology 146 9710595
2015 Meis2 is essential for cranial and cardiac neural crest development. BMC developmental biology 107 26545946
2013 Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate specification in the adult olfactory bulb. Development (Cambridge, England) 97 24284204
2013 Polycomb potentiates meis2 activation in midbrain by mediating interaction of the promoter with a tissue-specific enhancer. Developmental cell 95 24374176
2019 Polypyrimidine tract binding protein 1 promotes lymphatic metastasis and proliferation of bladder cancer via alternative splicing of MEIS2 and PKM. Cancer letters 86 30742945
1997 Meis2, a novel mouse Pbx-related homeobox gene induced by retinoic acid during differentiation of P19 embryonal carcinoma cells. Developmental dynamics : an official publication of the American Association of Anatomists 84 9337137
2000 Three-amino acid extension loop homeodomain proteins Meis2 and TGIF differentially regulate transcription. The Journal of biological chemistry 70 10764806
2009 Meis2 competes with the Groucho co-repressor Tle4 for binding to Otx2 and specifies tectal fate without induction of a secondary midbrain-hindbrain boundary organizer. Development (Cambridge, England) 68 19736326
2018 MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease. Clinical cancer research : an official journal of the American Association for Cancer Research 62 29716922
2019 Inhibition of Senescence-Associated Genes Rb1 and Meis2 in Adult Cardiomyocytes Results in Cell Cycle Reentry and Cardiac Repair Post-Myocardial Infarction. Journal of the American Heart Association 60 31315484
2008 Expression of FOXP2 in the developing monkey forebrain: comparison with the expression of the genes FOXP1, PBX3, and MEIS2. The Journal of comparative neurology 59 18461604
1997 Expression of Meis2, a Knotted-related murine homeobox gene, indicates a role in the differentiation of the forebrain and the somitic mesoderm. Developmental dynamics : an official publication of the American Association of Anatomists 58 9337138
2016 A Constitutive Intrinsic Inflammatory Signaling Circuit Composed of miR-196b, Meis2, PPP3CC, and p65 Drives Prostate Cancer Castration Resistance. Molecular cell 56 28041912
2014 MEIS2 is essential for neuroblastoma cell survival and proliferation by transcriptional control of M-phase progression. Cell death & disease 51 25210800
2015 MEIS2 involvement in cardiac development, cleft palate, and intellectual disability. American journal of medical genetics. Part A 50 25712757
2012 Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development. BMC developmental biology 46 22390724
2013 FOXC1 in human trabecular meshwork cells is involved in regulatory pathway that includes miR-204, MEIS2, and ITGβ1. Experimental eye research 43 23541832
2011 Cooperative transcriptional activation by Klf4, Meis2, and Pbx1. Molecular and cellular biology 42 21746878
2016 MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML. Cell reports 40 27346355
2014 Haploinsufficiency of MEIS2 is associated with orofacial clefting and learning disability. American journal of medical genetics. Part A 38 24678003
2018 MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1. Stem cell research & therapy 36 30526668
2016 De novo MEIS2 mutation causes syndromic developmental delay with persistent gastro-esophageal reflux. Journal of human genetics 34 27225850
2019 MEIS2 gene is responsible for intellectual disability, cardiac defects and a distinct facial phenotype. European journal of medical genetics 33 30735726
2018 Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability. European journal of human genetics : EJHG 33 30291340
2001 Cloning and developmental expression of a zebrafish meis2 homeobox gene. Mechanisms of development 33 11287203
2019 Hypermethylated and downregulated MEIS2 are involved in stemness properties and oxaliplatin-based chemotherapy resistance of colorectal cancer. Journal of cellular physiology 32 30859572
2022 Dlx1/2-dependent expression of Meis2 promotes neuronal fate determination in the mammalian striatum. Development (Cambridge, England) 31 35156680
2018 De novo missense variants in MEIS2 recapitulate the microdeletion phenotype of cardiac and palate abnormalities, developmental delay, intellectual disability and dysmorphic features. American journal of medical genetics. Part A 29 30055086
2010 Spatiotemporal distribution of PAX6 and MEIS2 expression and total cell numbers in the ganglionic eminence in the early developing human forebrain. Developmental neuroscience 29 20523026
2007 Expression of the homeodomain transcription factor Meis2 in the embryonic and postnatal retina. The Journal of comparative neurology 29 17729288
2015 miR-134 Modulates the Proliferation of Human Cardiomyocyte Progenitor Cells by Targeting Meis2. International journal of molecular sciences 27 26512644
2019 MEIS2 promotes cell migration and invasion in colorectal cancer. Oncology reports 25 31115559
2022 IGF2BP2 promotes the progression of ovarian endometriosis by regulating m6A-modified MEIS2 and GATA6. The international journal of biochemistry & cell biology 22 36113831
2020 The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice. The Journal of biological chemistry 22 32169905
2021 MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation. Cancers 21 34638267
2017 Meis2 as a critical player in MN1-induced leukemia. Blood cancer journal 21 28960191
2020 Neural crest cells require Meis2 for patterning the mandibular arch via the Sonic hedgehog pathway. Biology open 19 32616504
2010 An autoinhibitory effect of the homothorax domain of Meis2. The FEBS journal 19 20553494
2014 Differential expression of Meis2, Mab21l2 and Tbx3 during limb development associated with diversification of limb morphology in mammals. PloS one 18 25166052
2001 Cloning and expression of the TALE superclass homeobox Meis2 gene during zebrafish embryonic development. Mechanisms of development 17 11731263
2023 CircDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis. Epigenetics 16 36840946
2018 Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors. Stem cell reports 16 29641989
2021 Meis homeobox 2 (MEIS2) inhibits the proliferation and promotes apoptosis of thyroid cancer cell and through the NF-κB signaling pathway. Bioengineered 15 33975520
2019 The homeobox transcription factor MEIS2 is a regulator of cancer cell survival and IMiDs activity in Multiple Myeloma: modulation by Bromodomain and Extra-Terminal (BET) protein inhibitors. Cell death & disease 15 30975979
2018 Variant PRC1 competes with retinoic acid-related signals to repress Meis2 in the mouse distal forelimb bud. Development (Cambridge, England) 15 30190278
2021 LncRNA ILF3-AS1 promotes cell migration, invasion and EMT process in hepatocellular carcinoma via the miR-628-5p/MEIS2 axis to activate the Notch pathway. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 14 34053876
2015 RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression. Development (Cambridge, England) 14 26674308
2022 MicroRNA-18 facilitates the stemness of gastric cancer by downregulating HMGB3 though targeting Meis2. Bioengineered 12 35416122
2019 Epigenetic silencing of MEIS2 in prostate cancer recurrence. Clinical epigenetics 12 31640805
2021 Meis2 Is Required for Inner Ear Formation and Proper Morphogenesis of the Cochlea. Frontiers in cell and developmental biology 10 34124068
2015 Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb. EvoDevo 10 25861444
2021 Intellectual disability associated with craniofacial dysmorphism, cleft palate, and congenital heart defect due to a de novo MEIS2 mutation: A clinical longitudinal study. American journal of medical genetics. Part A 9 33427397
2015 Depletion of MEIS2 inhibits osteogenic differentiation potential of human dental stem cells. International journal of clinical and experimental medicine 8 26221261
2024 Touch receptor end-organ innervation and function require sensory neuron expression of the transcription factor Meis2. eLife 7 38386003
2021 A novel MEIS2 mutation explains the complex phenotype in a boy with a typical NF1 microdeletion syndrome. European journal of medical genetics 7 33722742
2020 MEIS2 sequence variant in a child with intellectual disability and cardiac defects: Expansion of the phenotypic spectrum and documentation of low-level mosaicism in an unaffected parent. American journal of medical genetics. Part A 7 33091211
2023 ERN1 dependent impact of glucose and glutamine deprivations on PBX3, PBXIP1, PAX6, MEIS1, and MEIS2 genes expression in U87 glioma cells. Endocrine regulations 6 36753664
2018 Meis2 represses the osteoblastic transdifferentiation of aortic valve interstitial cells through the Notch1/Twist1 pathway. Biochemical and biophysical research communications 6 30594396
2024 MEIS2 suppresses breast cancer development by downregulating IL10. Cancer reports (Hoboken, N.J.) 5 38711262
2023 LINC-PINT suppresses breast cancer cell proliferation and migration via MEIS2/PPP3CC/NF-κB pathway by sponging miR-576-5p. The American journal of the medical sciences 5 37660994
2022 The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice. Scientific reports 5 36418415
2025 LncRNA RMG controls liquid-liquid phase separation of MEIS2 to regulate myogenesis. International journal of biological macromolecules 4 40252346
2024 The neuronal transcription factor MEIS2 is a calpain-2 protease target. Journal of cell science 4 38305737
2022 Meis2 controls skeletal formation in the hyoid region. Frontiers in cell and developmental biology 4 36247013
2021 MEIS2 (15q14) gene deletions in siblings with mild developmental phenotypes and bifid uvula: documentation of mosaicism in an unaffected parent. Molecular cytogenetics 4 34930369
2009 Sonic hedgehog signaling in the chick retina accelerates Meis2 downregulation simultaneously with retinal ganglion cell genesis. Neuroreport 4 19188860
2025 Mesenchymal Meis2 controls whisker development independently from trigeminal sensory innervation. eLife 2 40183774
2024 Analysis of Meis2 knockout mice reveals Sonic hedgehog-mediated patterning of the cochlear duct. Developmental dynamics : an official publication of the American Association of Anatomists 2 39351969
2026 Comparative distribution of the hypothalamic neurons activated during wakefulness and paradoxical (REM) sleep using male TRAP2-red mice: contribution of orexin, MCH, Lhx6, and a new marker Meis2. Sleep 1 41313264
2025 Long read Nanopore sequencing identifies precise breakpoints of a de novo paracentric inversion that disrupt the MEIS2 gene in a Chinese girl with syndromic developmental delay. BMC pediatrics 1 39789493
2025 High-Grade Uterine Sarcoma: First Report of a MEIS2::FOXO4 Fusion. Genes, chromosomes & cancer 1 40249092
2026 OGT mediates O-GlcNAcylation of MEIS2 and affects palatal osteogenic development. International journal of oral science 0 41936590
2026 Meis1 and Meis2 are jointly required for advanced stages of mouse lens morphogenesis. Developmental biology 0 42000104
2026 Development of Chitosan-Carbon Dot Hybrid Nanoemulsomes for MEIS2 Inhibitor Delivery and Bioimaging in Colorectal Cancer. Life (Basel, Switzerland) 0 42073401
2025 MEIS2 Modulates Oxidative Phosphorylation and ROS Generation to Affect CD8+ T Cell Antitumor Immunity in Prostate Cancer. The Prostate 0 41031828
2025 Functional analysis of MEIS2 splice site variant c.438 + 1G>T in a congenital heart patient. Frontiers in genetics 0 41080700
2025 CDK4/6 Inhibition Reverses MEIS2 Suppression of CRL4 CRBN to Enhance Immunomodulatory Drug Therapy in Multiple Myeloma. bioRxiv : the preprint server for biology 0 41279046
2025 Developmental and adult expression of the Meis2 transcription factor in the central nervous system of Xenopus laevis: a developmental and evolutive analysis. Frontiers in neuroanatomy 0 41280242
2024 Multi-omics analysis detail a submicroscopic inv(15)(q14q15) generating fusion transcripts and MEIS2 and NUSAP1 haploinsufficiency. Scientific reports 0 39639090
2024 Cleft palate, congenital heart disease, and developmental delay involving MEIS2 heterozygous mutations found in the patient with attention deficit hyperactivity disorder: a case report. Frontiers in pediatrics 0 39776641
2020 Placental Expression of the Forelimb Patterning Transcription Factor MEIS2 in Trisomy 15. Fetal and pediatric pathology 0 32138576

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