Affinage

MEIS2

Homeobox protein Meis2 · UniProt O14770

Length
477 aa
Mass
51.8 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MEIS2 is a TALE-class homeodomain transcription factor that functions as a context-dependent transcriptional activator by forming heterodimeric and trimeric complexes with PBX1, HOX-class proteins, and tissue-specific partners (Otx2, Pax3/7, Pax6, Dlx2, Klf4, SHOX2) to regulate target genes in diverse developmental and adult contexts including limb proximal-distal patterning, midbrain tectal specification, striatal medium spiny neuron differentiation, adult SVZ neurogenesis, craniofacial/cardiac neural crest morphogenesis, and low-threshold mechanoreceptor maturation (PMID:10619030, PMID:19736326, PMID:35156680, PMID:24284204, PMID:26545946, PMID:38386003). Its transcriptional output is controlled by autoinhibition of its C-terminal activation domain by the Hth domain (relieved by PBX1 binding), competition with co-repressors such as Groucho/Tle4 and TGIF, and Polycomb (RING1B/PRC1)-dependent chromatin topology that gates locus activation in response to retinoic acid signaling (PMID:20553494, PMID:19736326, PMID:10764806, PMID:24374176, PMID:26674308). MEIS2 protein abundance and nuclear accumulation are regulated by multilayered post-translational mechanisms: arginine methylation controls CRM1-dependent nuclear export, O-GlcNAcylation at Ser237 stabilizes MEIS2 by blocking ubiquitination, calpain-2-mediated proteolytic cleavage limits full-length protein in stem/progenitor cells, and MEIS2 serves as a substrate of the CRL4-CRBN E3 ubiquitin ligase displaced by immunomodulatory drugs (PMID:29641989, PMID:41936590, PMID:38305737, PMID:30975979). MEIS2 directly activates genes including FOXM1, doublecortin, tyrosine hydroxylase, Zfp503, Six3, and osteogenic loci, and is required for chromatin accessibility at its target sites (PMID:25210800, PMID:24284204, PMID:35156680, PMID:32169905).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing MEIS2 as a transcription factor capable of trimeric complex formation with PBX and HOX-class partners answered how a TALE-homeodomain protein achieves tissue-specific transcriptional switching—here converting PDX1 from beta-cell to acinar-type activation.

    Evidence Co-IP, EMSA, and reporter assays reconstituting the MEIS2–PBX1b–PDX1 trimeric complex on the elastase I enhancer B element in pancreatic cell lines

    PMID:9710595

    Open questions at the time
    • Trimeric complex demonstrated only on one enhancer element
    • Structural basis for partner selectivity unknown
    • In vivo relevance for pancreatic cell fate not tested genetically
  2. 1999 High

    Demonstrating that Meis2 expression is restricted to proximal limb and that ectopic expression represses distal limb genes established MEIS2 as a spatial determinant of proximal-distal limb identity, a role later shown to be Polycomb-regulated.

    Evidence Ectopic Meis2 expression in chick limb bud with epistasis to BMPs and Hoxd genes; in situ hybridization

    PMID:10619030

    Open questions at the time
    • Downstream targets in limb not identified at this stage
    • Mechanism of BMP/Hoxd-mediated repression of Meis2 unclear
  3. 2000 High

    Identification of MEIS2 isoforms activating the dopamine D1A receptor promoter, and competition by TGIF on the same DNA sites, revealed a splice-variant-based regulatory logic including dominant-negative inhibition by Meis2e.

    Evidence EMSA, reporter assays across multiple cell lines, and co-expression competition assays with TGIF and Meis2e

    PMID:10764806

    Open questions at the time
    • Physiological contexts where Meis2e exerts dominant-negative function in vivo uncharacterized
    • Full repertoire of direct DNA targets unknown
  4. 2009 High

    Showing that Meis2 competes with the Groucho co-repressor Tle4 for Otx2 binding to relieve transcriptional repression defined the mechanism by which MEIS2 specifies tectal fate—functioning not solely as a DNA-binding activator but as a co-factor competition switch.

    Evidence In ovo electroporation gain/loss-of-function, reciprocal Co-IP competition assays, Otx2-dependent reporter

    PMID:19736326

    Open questions at the time
    • Whether this competition mechanism operates in mammalian midbrain unknown
    • Direct target genes downstream of Otx2-Meis2 in tectum not defined
  5. 2010 Medium

    Discovery that the Hth domain autoinhibits MEIS2's C-terminal activation domain and that PBX1 binding partially relieves this autoinhibition revealed an intrinsic regulatory switch gating transcriptional output on PBX dimerization.

    Evidence Domain deletion/mutation analysis with transcriptional reporter readouts; comparison with Meis3.2 splice variant

    PMID:20553494

    Open questions at the time
    • Structural basis for autoinhibition not resolved
    • Whether other partners besides PBX1 relieve autoinhibition untested
    • Single-lab finding
  6. 2011 High

    Identification of a MEIS2–PBX1–KLF4 cooperative complex that activates p15(Ink4a) and E-cadherin expanded the partner repertoire beyond HOX-class proteins and linked MEIS2 to cell cycle control.

    Evidence Reciprocal Co-IP, reporter assays, siRNA knockdown with S-phase entry readout

    PMID:21746878

    Open questions at the time
    • Whether this complex operates in normal development or only in tumor suppression unclear
    • Genome-wide target landscape of MEIS2–KLF4 not mapped
  7. 2013 High

    Two concurrent advances established (i) a Meis2–Pax6–Dlx2 complex driving adult SVZ neurogenesis with direct ChIP-validated targets (doublecortin, tyrosine hydroxylase), and (ii) a RING1B-dependent chromatin topology mechanism (promoter–enhancer–RBS tripartite loop) gating Meis2 locus activation during midbrain development.

    Evidence (i) Retroviral dominant-negative and siRNA in vivo, ChIP, Co-IP in adult SVZ; (ii) 3C/4C, ChIP, conditional KO mice, transgenic reporters

    PMID:24284204 PMID:24374176

    Open questions at the time
    • Whether the Pax6–Dlx2–Meis2 complex acts identically in embryonic and adult neurogenesis untested
    • How RING1B release is triggered at the molecular level remains unclear
  8. 2014 High

    Demonstrating that MEIS2 directly drives FOXM1 and the MuvB–BMYB–FOXM1 mitotic gene program in neuroblastoma revealed a role for MEIS2 in M-phase progression beyond developmental transcription.

    Evidence siRNA depletion, ChIP on FOXM1 promoter, gene expression profiling, proliferation/tumorigenicity assays

    PMID:25210800

    Open questions at the time
    • Whether the FOXM1 axis is relevant in normal proliferating progenitors unknown
    • MEIS2 co-factors in this context not identified
  9. 2015 High

    Conditional inactivation in neural crest cells causing persistent truncus arteriosus, craniofacial skeletal defects, and cranial nerve abnormalities, combined with epistasis showing RING1A/B represses Meis2 in distal limb, consolidated MEIS2 as essential for neural crest-derived tissue morphogenesis and confirmed Polycomb as a gate for Meis2 domain control in limb patterning.

    Evidence Neural crest-specific conditional KO mice (AP2α-Cre), Ring1A/B double KO with Meis2 rescue deletion, ChIP, in situ hybridization

    PMID:26545946 PMID:26674308

    Open questions at the time
    • Direct target genes mediating cardiac outflow tract septation not identified
    • Whether MEIS2 acts cell-autonomously in all affected neural crest lineages not resolved
  10. 2018 High

    Discovery that arginine methylation on a conserved residue blocks CRM1-mediated nuclear export (without affecting PBX1 binding) introduced post-translational control of MEIS2 subcellular localization as a mechanism coupling EGFR signaling to neuronal differentiation, while variant PRC1 (PCGF3/5) was shown to set the RA-signaling threshold for Meis2 activation in limb.

    Evidence Site-directed mutagenesis, Co-IP of MEIS2–CRM1 and MEIS2–PBX1, cell fractionation, neuronal differentiation assay; PcG conditional KOs with mathematical modeling

    PMID:29641989 PMID:30190278

    Open questions at the time
    • Identity of the arginine methyltransferase responsible unknown
    • How EGFR signaling controls methylation status not mapped
  11. 2019 High

    Identification of MEIS2 as a CRL4-CRBN E3 ligase substrate displaced by immunomodulatory drugs (IMiDs) revealed a pharmacologically relevant degradation axis, while calpain-2 cleavage sensitivity—modulated by phosphorylation and PBX1 dimerization—provided a second proteolytic layer controlling MEIS2 levels in progenitor cells.

    Evidence Crystal structure reference for CRBN interaction, siRNA in myeloma cells; in vitro calpain-2 cleavage reconstitution (reported fully in 2024), mutagenesis of phosphorylation/dimerization sites

    PMID:30975979 PMID:38305737

    Open questions at the time
    • Relative contributions of CRL4-CRBN vs. calpain-2 degradation in non-cancer contexts unresolved
    • Calpain-2 cleavage site(s) not precisely mapped
  12. 2020 High

    Genome-wide ChIP-seq and ATAC-seq in the developing palate demonstrated that MEIS2 directly occupies and is required for chromatin accessibility at osteogenic gene loci, with SHOX2 as a physical co-occupant, providing the first genome-wide mechanistic view of MEIS2 chromatin function in craniofacial osteogenesis.

    Evidence Conditional KO mice (Wnt1-Cre), ChIP-seq, ATAC-seq, RNA-seq, Co-IP for MEIS2–SHOX2, rescue experiments

    PMID:32169905

    Open questions at the time
    • Whether MEIS2 acts as a pioneer factor or requires pre-existing accessibility not tested
    • SHOX2 contribution to co-occupied sites not dissected genetically
  13. 2022 High

    Demonstration that Meis2 directly binds Zfp503 and Six3 promoters and is required for striatal MSN differentiation, with Dlx1/2 acting upstream via the hs599 enhancer, established a complete genetic circuit for MEIS2-dependent ventral forebrain neuronal specification.

    Evidence Conditional KO mice, ChIP at Zfp503 and Six3 promoters, in situ hybridization, cell quantification

    PMID:35156680

    Open questions at the time
    • Whether MEIS2 partners (PBX, Dlx) co-occupy these promoters in striatum not tested
    • How D1 vs D2 MSN subtype specification diverges downstream of Meis2 unknown
  14. 2024 High

    Two studies extended MEIS2 biology to peripheral somatosensory neurons and to proteolytic regulation: Meis2 loss in LTMRs impaired end-organ innervation, electrophysiology, and touch behavior without affecting cell survival, while calpain-2 was biochemically reconstituted as a direct MEIS2 protease whose cleavage sensitivity is tuned by phosphorylation and PBX1 binding.

    Evidence LTMR-specific conditional KO with electrophysiology, EM, behavioral assays, transcriptomics; in vitro calpain-2 cleavage with recombinant proteins, mutagenesis, neuronal differentiation in adult V-SVZ

    PMID:38305737 PMID:38386003

    Open questions at the time
    • Target genes controlled by MEIS2 in LTMRs not validated by ChIP
    • Whether calpain-2 regulation of MEIS2 operates beyond SVZ neurogenesis untested
  15. 2026 High

    O-GlcNAcylation at Ser237 was identified as a stabilizing modification that blocks MEIS2 ubiquitination, linking OGT activity to palatal bone formation and providing a third post-translational axis (alongside arginine methylation and calpain cleavage) controlling MEIS2 protein levels.

    Evidence Mass spectrometry for O-GlcNAc site, Ser237 mutagenesis, ubiquitination assay, zebrafish in vivo validation

    PMID:41936590

    Open questions at the time
    • Whether Ser237 O-GlcNAcylation and CRL4-CRBN ubiquitination converge on the same lysine residues unknown
    • OGT upstream signals in palatal mesenchyme not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis for MEIS2 partner selectivity across developmental contexts, the identity of the arginine methyltransferase controlling nuclear export, the precise calpain-2 cleavage site(s), genome-wide target landscapes in most tissues, and whether MEIS2 liquid-liquid phase separation has functional significance in vivo.
  • No crystal structure of MEIS2 in complex with any partner
  • Arginine methyltransferase identity unknown
  • Calpain-2 cleavage site(s) not mapped at residue level
  • LLPS biology based on a single low-confidence study

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 7
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 10 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-112316 Neuronal System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 3
Partners
CRBNDLX2KLF4OTX2PAX3PAX6PBX1SHOX2
Complex memberships
MEIS2–PBX1 heterodimerMEIS2–PBX1–PDX1 trimerMEIS2–Pax6–Dlx2 complex

Evidence

Reading pass · 31 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-type; beta-cell lines lack PBX1b and MRG1, preventing trimeric complex formation. Co-immunoprecipitation, gel mobility shift assays, transcriptional reporter assays in cell lines, site-directed mutagenesis of B element Molecular and cellular biology High 9710595
1998 MEIS2 (MRG1) is a transcriptional activator; its transformation activity requires cytokine induction via the JAK/STAT signaling pathway, and mutations in the Box1 (JAK1-binding) motif or STAT3-binding region of the IL-9 receptor abolish MRG1 induction by IL-9. mRNA differential display, deletion/point mutations of IL-9 receptor domains, transfection assays, soft agar and nude mouse tumor assays Proceedings of the National Academy of Sciences of the United States of America Medium 9811838
1999 Meis2 expression restricted to proximal limb bud is essential for normal limb outgrowth; ectopic Meis2 represses distal limb genes, and BMPs together with Hoxd genes restrict Meis2 to the proximal domain, establishing a proximal-distal regulatory axis. Ectopic expression in chick limb bud, in situ hybridization, genetic epistasis with BMPs and Hoxd genes Molecular cell High 10619030
2000 MEIS2 isoforms (a-d) activate the D1A dopamine receptor promoter by binding the ACT element; TGIF competes with MEIS2 for the same DNA sites and represses MEIS2-induced transcription activation. Splice variant Meis2e (truncated homeodomain) cannot bind DNA or activate transcription but acts as a dominant-negative inhibitor of Meis2d. Gel mobility shift assays, transcriptional reporter assays in multiple cell lines, co-expression competition assays, in situ hybridization The Journal of biological chemistry High 10764806
2009 Meis2 is necessary and sufficient for tectal development in chick; Meis2 competes with the Groucho co-repressor Tle4 (Grg4) for binding to Otx2, thereby relieving Otx2 transcriptional repression and restoring Otx2 activator function to specify tectal fate. In ovo electroporation (gain- and loss-of-function), Otx2-dependent reporter assay, co-immunoprecipitation/competition binding assays Development (Cambridge, England) High 19736326
2010 The homothorax (Hth) domain of Meis2 autoinhibits its C-terminal transcriptional activation domain; binding of Pbx1 to the Hth domain partially relieves this autoinhibition. The Meis3.2 splice-equivalent deletion within the Hth domain derepresses the activation domain and weakens Pbx1 interaction. Transcriptional reporter assays, domain deletion/mutation analysis, protein interaction assays, bioinformatics The FEBS journal Medium 20553494
2011 Meis2 and Pbx1 physically interact with Klf4 and are co-recruited to promoter elements containing adjacent Klf4/GC-box and Meis/Pbx sites to cooperatively activate p15(Ink4a) and E-cadherin transcription; the Meis2d activation domain is required for full cooperative activation. Co-immunoprecipitation, transcriptional reporter assays, siRNA knockdown with cell cycle readout (S-phase entry), bioinformatics Molecular and cellular biology High 21746878
2012 Meis2 physically interacts with Pax3 and Pax7 in the tectal anlage; Meis2 acts downstream of Pax3/7, and Pax3 and Pax7 mutually regulate each other's expression and modulate Meis2 expression levels in the chick mesencephalic vesicle. In ovo electroporation (gain/loss-of-function), co-immunoprecipitation, in situ hybridization BMC developmental biology Medium 22390724
2013 Meis2 forms a complex with Pax6 and Dlx2 in adult olfactory bulb neurogenesis; Meis2 activity is cell-autonomously required for neuronal fate acquisition by SVZ-derived progenitors and for dopaminergic periglomerular neuron generation. Direct Meis2 targets identified by ChIP include doublecortin and tyrosine hydroxylase. Retroviral expression of dominant-negative forms and siRNA in vivo; chromatin immunoprecipitation (ChIP); biochemical co-immunoprecipitation of the Meis2-Pax6-Dlx2 complex Development (Cambridge, England) High 24284204
2013 Polycomb RING1B binds the Meis2 promoter and a 3'-end RING1B-binding site (RBS) to maintain repression; during midbrain development, a midbrain-specific enhancer (MBE) transiently forms a promoter-MBE-RBS tripartite interaction in a RING1-dependent manner, after which RING1B-bound RBS dissociates, leaving promoter-MBE engagement to activate Meis2 expression. Chromosome conformation capture (3C/4C), ChIP, conditional knockout mice, transgenic reporter assays Developmental cell High 24374176
2014 MEIS2 is required for neuroblastoma cell survival and M-phase progression; MEIS2 transcriptionally activates the MuvB-BMYB-FOXM1 complex and directly drives FOXM1 expression to upregulate mitotic genes. siRNA depletion, ectopic overexpression, gene expression profiling, ChIP, in vitro proliferation/tumorigenicity assays Cell death & disease High 25210800
2015 Meis2 is required for cranial and cardiac neural crest cell development; conditional inactivation using AP2α-IRES-Cre results in persistent truncus arteriosus, craniofacial skeletal defects, and cranial nerve abnormalities, establishing Meis2 as essential for neural crest-derived tissues. Conditional knockout mice (systemic and neural crest-specific via AP2α-Cre), histology, immunohistochemistry BMC developmental biology High 26545946
2015 RING1A/B (PRC1) directly binds and represses Meis1/2 in the distal forelimb bud; additional deletion of Meis2 in Ring1A/B-deficient mice partially restores distal gene expression and limb formation, placing RING1-dependent Meis2 repression as a necessary step for proximal-distal specification. Conditional double knockout mice (Ring1A/B), epistasis rescue by additional Meis2 deletion, in situ hybridization, ChIP Development (Cambridge, England) High 26674308
2016 MEIS2 is highly expressed in AML1-ETO-positive AML cells and is required for their growth; MEIS2 directly binds the Runt domain of AML1-ETO (shown by Co-IP), and high MEIS2 impairs repressive DNA binding of AML1-ETO, leading to increased expression of YES1. Co-immunoprecipitation (MEIS2–AML1-ETO Runt domain), shRNA knockdown, mouse leukemia model, gene expression analysis Cell reports High 27346355
2016 A constitutively active feedforward circuit composed of IκBα/NF-κB(p65), miR-196b-3p, Meis2, and PPP3CC drives castration-resistant prostate cancer; Meis2 is a downstream target of miR-196b-3p suppression and is part of this circuit that controls stem cell transcription factor expression. Reporter assays, miRNA target validation, knockdown experiments, mouse xenograft models Molecular cell Medium 28041912
2018 MEIS2 nuclear localization in adult SVZ progenitors is regulated by arginine methylation on a conserved arginine residue; methylation impairs interaction with the nuclear export receptor CRM1 without affecting PBX1 dimerization, thereby allowing MEIS2 nuclear accumulation required for neuronal differentiation. Downregulation of EGFR signaling triggers this methylation. Mutagenesis of arginine residue, Co-IP (MEIS2–CRM1 and MEIS2–PBX1), cell fractionation, retroviral overexpression, neuronal differentiation assay Stem cell reports High 29641989
2018 MEIS2 regulates endothelial-to-hematopoietic transition (EHT) from human embryonic stem cells; MEIS2 deletion suppresses hemogenic endothelial specification and EHT. TAL1 acts as a downstream gene mediating MEIS2 function during early hematopoiesis. CRISPR/Cas9 knockout in hESCs, hematopoietic differentiation assays, gene expression analysis Stem cell research & therapy Medium 30526668
2019 PTBP1 upregulates the MEIS2-L splice variant (via alternative mRNA splicing) to promote bladder cancer cell migration and invasion; overexpression of MEIS2-L rescues oncogenic migration/invasion abilities and MMP9 expression after PTBP1 knockdown. siRNA knockdown, splicing variant overexpression rescue experiments, in vitro migration/invasion assays, in vivo lymph node metastasis model Cancer letters Medium 30742945
2019 MEIS2 is a substrate of the CRL4-cereblon (CRL4CRBN) E3 ubiquitin ligase; IMiDs block MEIS2 from binding CRBN, facilitating CRL4CRBN-IMiD E3-ubiquitin ligase activity and proteasome-mediated degradation of target substrates. MEIS2 also regulates Cyclin E/CCNE1 and NKG2D/DNAM-1 NK-cell ligand expression in multiple myeloma cells. siRNA knockdown, crystallographic identification of MEIS2-CRBN interaction (referenced), apoptosis and proliferation assays, BET inhibitor treatment Cell death & disease Medium 30975979
2019 Silencing of both Rb1 and Meis2 by siRNA in adult cardiomyocytes promotes cell cycle re-entry; simultaneous knockdown results in increased proliferation markers (EdU, PH3, Ki67, Aurora B), reduced cardiomyocyte size, increased mononucleation, and improved cardiac function post-myocardial infarction in vivo, identifying Meis2 as a senescence-associated cell cycle inhibitor in cardiomyocytes. siRNA knockdown in isolated adult rat cardiomyocytes and hiPSC-derived cardiomyocytes, hydrogel-based in vivo delivery post-MI, immunofluorescence for proliferation markers, echocardiography Journal of the American Heart Association Medium 31315484
2020 MEIS2 directly binds chromatin of osteogenic gene loci (identified by ChIP-seq) and is required for chromatin accessibility of osteogenic genes (ATAC-seq) in the developing palate; MEIS2 physically interacts with SHOX2 and co-occupies osteogenic gene loci genome-wide. MEIS2 is required for palatal bone formation downstream of neural crest cell specification. Conditional KO mice (Wnt1-Cre), ChIP-seq, RNA-seq, ATAC-seq, Co-IP (MEIS2–SHOX2 interaction), rescue experiments The Journal of biological chemistry High 32169905
2018 Variant PRC1 incorporating PCGF3 and PCGF5 represses Meis2 in the distal forelimb bud; PcG factors and retinoic acid-related signals antagonize each other to polarize Meis2 expression along the proximal-distal axis, with PcG adjusting the threshold for RA signaling to regulate Meis2. Mouse genetics (conditional knockouts), mathematical modeling, ChIP, in situ hybridization Development (Cambridge, England) Medium 30190278
2018 MEIS2 nuclear localization is regulated post-translationally; arginine methylation on a conserved residue close to nested CRM1- and PBX1-binding sites controls nuclear/cytoplasmic partitioning. In the adult V-SVZ, high calpain-2 activity in stem/progenitor cells cleaves MEIS2, and reduced calpain-2 activity during neuronal differentiation stabilizes MEIS2 full-length protein. Site-directed mutagenesis of arginine, Co-IP, fractionation; calpain-2 substrate identification by in vitro cleavage and mass spectrometry (described in 2024 paper but methylation result 2018) Stem cell reports High 29641989
2024 MEIS2 is a direct substrate of the intracellular protease calpain-2 (CAPN2/CAPNS1); phosphorylation at conserved serine/threonine residues or dimerization with PBX1 reduces MEIS2 sensitivity to calpain-2 cleavage. High calpain-2 activity in adult V-SVZ stem/progenitor cells degrades MEIS2, and its decline during differentiation allows MEIS2 full-length accumulation needed for neuronal fate. Blocking calpain-2 or expressing cleavage-insensitive MEIS2 increases neuron production. In vitro protease cleavage assay with recombinant calpain-2, mutagenesis of phosphorylation/dimerization sites, Co-IP, overexpression of catalytically active CAPN2, neuronal differentiation assays in adult V-SVZ Journal of cell science High 38305737
2022 Meis2 directly binds the Zfp503 and Six3 promoters and is required for their expression; Dlx1/2 drives Meis2 expression in LGE progenitors at least partly through the hs599 enhancer. Loss of Meis2 blocks striatal medium spiny neuron (MSN) differentiation, reducing D1 and D2 MSNs. Conditional KO mice (Meis2 deletion), ChIP to show direct promoter binding of Zfp503 and Six3, in situ hybridization, cell counting Development (Cambridge, England) High 35156680
2024 Meis2 is specifically expressed in cutaneous low-threshold mechanoreceptors (LTMRs) in mice, dependent on target-derived signals. Conditional loss of Meis2 in LTMRs does not affect their survival or initial specification but markedly impairs end-organ innervation morphology, electrophysiological properties, and transcriptome, resulting in impaired light touch behavioral responses. Conditional KO mice (LTMR-specific), electrophysiology, electron/confocal microscopy of end-organ morphology, behavioral assays, transcriptome profiling eLife High 38386003
2020 Meis2 conditional inactivation in neural crest cells (Wnt1-Cre) causes loss of Sonic hedgehog (Shh) signaling in oropharyngeal epithelium, impaired patterning of the first pharyngeal arch along lateral-medial and oral-aboral axes, and hypoplastic tongue with ectopic mandibular ossification. Conditional KO mice (Wnt1-Cre;Meis2fl/fl), in situ hybridization, immunohistochemistry for Shh pathway components and pharyngeal arch markers Biology open Medium 32616504
2024 Meis2 loss-of-function in the cochlea leads to a phenotype resembling Shh mutants, with loss of apically expressed cochlear genes and ectopic/extra rows of sensory hair cells; Meis2 ChIP-seq in an otic cell line identifies direct target genes involved in Shh-mediated cochlear patterning. Conditional KO mice, gene expression profiling, ChIP-seq in otic cell line Developmental dynamics Medium 39351969
2025 CDK4/6 inhibition rapidly accelerates IMiD-mediated displacement of MEIS2 from CRBN and destabilizes MEIS2 protein while increasing CRBN levels, enhancing CRL4CRBN ubiquitination of IKZF3/IKZF1 for degradation. MEIS2 also promotes BCMA expression and antagonizes BCMA repression by IMiD/CELMoD, providing a survival signal in myeloma cells. Biochemical displacement assays, protein stability assays, ubiquitination assays, Co-IP, cell viability and apoptosis assays in bone marrow myeloma cells bioRxivpreprint Medium 41279046
2026 OGT mediates O-GlcNAcylation of MEIS2 at serine 237, which maintains MEIS2 protein stability by inhibiting its ubiquitination; loss of O-GlcNAc in zebrafish results in elevated cleft palate prevalence and impaired palatal bone formation. O-GlcNAcylation of MEIS2 maintains osteogenic homeostasis in palatal development. Mass spectrometry identification of O-GlcNAcylation site, site-directed mutagenesis (Ser237), ubiquitination assay, zebrafish loss-of-function, protein stability assay International journal of oral science High 41936590
2025 LncRNA RMG regulates myogenesis by modulating liquid-liquid phase separation (LLPS) of MEIS2; lnc-RMG produces miR-133a-3p which targets and inhibits MEIS2 expression, thereby inhibiting MEIS2 LLPS. This inhibition promotes TGFβR2 transcription to regulate myogenesis. lncRNA knockdown, miRNA overexpression, LLPS assay for MEIS2, luciferase reporter, qPCR/western blot, skeletal muscle regeneration model International journal of biological macromolecules Low 40252346

Source papers

Stage 0 corpus · 100 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 250 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 103 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
1998 MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity. Proceedings of the National Academy of Sciences of the United States of America 92 9811838
2019 Polypyrimidine tract binding protein 1 promotes lymphatic metastasis and proliferation of bladder cancer via alternative splicing of MEIS2 and PKM. Cancer letters 85 30742945
2014 Regulation of arabidopsis flowering by the histone mark readers MRG1/2 via interaction with CONSTANS to modulate FT expression. PLoS genetics 84 25211338
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 59 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
1997 MSG1 and its related protein MRG1 share a transcription activating domain. Gene 55 9434189
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
1999 Molecular cloning and chromosomal localization of the human CITED2 gene encoding p35srj/Mrg1. Genomics 47 10552932
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
2007 MRG-1, an autosome-associated protein, silences X-linked genes and protects germline immortality in Caenorhabditis elegans. Development (Cambridge, England) 42 17215300
2016 MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML. Cell reports 39 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 35 30526668
2016 De novo MEIS2 mutation causes syndromic developmental delay with persistent gastro-esophageal reflux. Journal of human genetics 34 27225850
2020 MRG1/2 histone methylation readers and HD2C histone deacetylase associate in repression of the florigen gene FT to set a proper flowering time in response to day-length changes. The New phytologist 33 32315442
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
2022 Dlx1/2-dependent expression of Meis2 promotes neuronal fate determination in the mammalian striatum. Development (Cambridge, England) 31 35156680
2019 Hypermethylated and downregulated MEIS2 are involved in stemness properties and oxaliplatin-based chemotherapy resistance of colorectal cancer. Journal of cellular physiology 30 30859572
2002 MRG-1, a mortality factor-related chromodomain protein, is required maternally for primordial germ cells to initiate mitotic proliferation in C. elegans. Mechanisms of development 30 12175490
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 Proteasome regulation of the chromodomain protein MRG-1 controls the balance between proliferative fate and differentiation in the C. elegans germ line. Development (Cambridge, England) 27 25564623
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 24 31115559
2011 The chromodomain protein MRG-1 facilitates SC-independent homologous pairing during meiosis in Caenorhabditis elegans. Developmental cell 24 22172672
2000 MRG1 expression in fibroblasts is regulated by Sp1/Sp3 and an Ets transcription factor. The Journal of biological chemistry 23 11114295
2020 The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice. The Journal of biological chemistry 22 32169905
2017 Meis2 as a critical player in MN1-induced leukemia. Blood cancer journal 21 28960191
2022 IGF2BP2 promotes the progression of ovarian endometriosis by regulating m6A-modified MEIS2 and GATA6. The international journal of biochemistry & cell biology 20 36113831
2021 MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation. Cancers 20 34638267
2020 The histone methylation readers MRG1/MRG2 and the histone chaperones NRP1/NRP2 associate in fine-tuning Arabidopsis flowering time. The Plant journal : for cell and molecular biology 19 32324922
2010 An autoinhibitory effect of the homothorax domain of Meis2. The FEBS journal 19 20553494
2020 Neural crest cells require Meis2 for patterning the mandibular arch via the Sonic hedgehog pathway. Biology open 18 32616504
2014 Differential expression of Meis2, Mab21l2 and Tbx3 during limb development associated with diversification of limb morphology in mammals. PloS one 17 25166052
2001 Cloning and expression of the TALE superclass homeobox Meis2 gene during zebrafish embryonic development. Mechanisms of development 17 11731263
2018 Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors. Stem cell reports 16 29641989
2024 Histone methylation readers MRG1/2 interact with PIF4 to promote thermomorphogenesis in Arabidopsis. Cell reports 15 38308844
2023 CircDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis. Epigenetics 15 36840946
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
2005 Functional analysis of MRG-1: the ortholog of human MRG15 in Caenorhabditis elegans. The journals of gerontology. Series A, Biological sciences and medical sciences 14 15972600
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
2012 MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells. Cell research 10 22212480
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 Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb. EvoDevo 9 25861444
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
2023 Histone methylation readers MRG1/MRG2 interact with the transcription factor TCP14 to positively modulate cytokinin sensitivity in Arabidopsis. Journal of genetics and genomics = Yi chuan xue bao 7 36870415
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
2022 SUMOylation of the chromodomain factor MRG-1 in C. elegans affects chromatin-regulatory dynamics. BioTechniques 6 35698829
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
2022 The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice. Scientific reports 5 36418415
1994 MRG1-1, a dominant allele that confers methomyl resistance in yeast expressing the cytoplasmic male sterility T-urf13 gene from maize. Current genetics 5 7874742
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
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 4 37660994
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
2019 MRG-1 is required for both chromatin-based transcriptional silencing and genomic integrity of primordial germ cells in Caenorhabditis elegans. Genes to cells : devoted to molecular & cellular mechanisms 3 30929290
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
2015 Restricted distribution of mrg-1 mRNA in C. elegans primordial germ cells through germ granule-independent regulation. Genes to cells : devoted to molecular & cellular mechanisms 1 26537333
1995 Detection of a glycosphingolipid antigen in bladder cancer cells with monoclonal antibody MRG-1. The Histochemical journal 1 7797428
2026 OGT mediates O-GlcNAcylation of MEIS2 and affects palatal osteogenic development. International journal of oral science 0 41936590
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
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