Affinage

PAX5

Paired box protein Pax-5 · UniProt Q02548

Length
391 aa
Mass
42.1 kDa
Annotated
2026-04-29
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAX5 is a paired-box transcription factor that serves as the master regulator of B-lymphocyte lineage identity, continuously required from the pro-B cell stage onward to enforce B-cell commitment, prevent alternative lineage differentiation, and block premature plasma cell differentiation (PMID:10524629, PMID:12098702, PMID:16546097). PAX5 activates B-cell-specific genes (CD19, BLNK, RAG2, hTERT) by recruiting SWI/SNF chromatin-remodeling complexes and inducing enhancer formation, while repressing lineage-inappropriate genes (Notch1, PRDM1/Blimp1, Wapl) through recruitment of Groucho/Grg corepressors and Polycomb Repressive Complex 2 (PMID:1375324, PMID:10811620, PMID:19549820, PMID:17682124, PMID:32612238). PAX5 controls V(D)J recombination at the immunoglobulin loci by repressing the cohesin-release factor Wapl to enable cohesin-driven loop extrusion and IgH locus contraction, and by physically interacting with the RAG1–RAG2 complex to enhance recombination signal sequence cleavage at VH gene segments (PMID:32612238, PMID:16680144, PMID:15004008). Germline and somatic PAX5 mutations, including the recurrent P80R variant, drive B-cell acute lymphoblastic leukemia through impaired B-lymphoid development and altered enhancer regulation (PMID:30643249, PMID:36516256).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 High

    Identifying PAX5/BSAP as a direct transcriptional activator of CD19 established it as a sequence-specific DNA-binding transcription factor with B-cell-restricted function.

    Evidence In vitro DNA binding, in vivo footprinting, and reporter assays showing PAX5 occupies the CD19 promoter in B cells but not plasma or HeLa cells

    PMID:1375324

    Open questions at the time
    • Genome-wide target repertoire unknown
    • Mechanism of B-cell specificity of PAX5 expression not addressed
  2. 1996 Medium

    Demonstration that PAX5 acts as both activator and repressor in a concentration- and context-dependent manner expanded its functional repertoire beyond simple activation.

    Evidence Reporter assays showing PAX5 represses J chain via promoter binding, relieved by IL-2-induced PAX5 downregulation; affinity measurements showing activator motifs have ~20-fold higher binding affinity than repressor motifs

    PMID:8885870 PMID:9506950

    Open questions at the time
    • Cofactors mediating repression not yet identified
    • In vivo relevance of concentration-dependent switching not tested
  3. 1999 High

    The discovery that Pax5-deficient pro-B cells can reconstitute T-cell development proved that PAX5 is the commitment factor for B-lymphocyte lineage identity, resolving the question of when and how B-cell fate is locked in.

    Evidence Pax5−/− pro-B cells adoptively transferred into RAG2−/− mice gave rise to T cells in vivo

    PMID:10524629

    Open questions at the time
    • Whether Pax5 is continuously required after commitment not yet shown
    • Direct repression targets maintaining lineage identity unknown
  4. 2000 High

    Identification of Groucho/Grg4 as a Pax5-recruited corepressor provided the first mechanistic basis for PAX5-mediated transcriptional repression, acting through the octapeptide motif.

    Evidence Yeast two-hybrid, co-immunoprecipitation, domain mapping, and reporter assays in B cell lines

    PMID:10811620

    Open questions at the time
    • Identity of endogenous repressed target genes bound by Pax5-Grg complexes unknown
    • In vivo requirement for octapeptide-Grg interaction not tested
  5. 2002 High

    Conditional deletion proved PAX5 is continuously required to maintain B-cell identity — not just for initial commitment — and identified key activation targets (BLNK for pre-BCR signaling) and repression targets (Notch1 for T-cell block).

    Evidence Conditional Pax5 deletion in committed pro-B cells caused multilineage reprogramming in vivo; BLNK rescue restored pre-BCR signaling; Pax5 knockin at the Ikaros locus repressed Notch1

    PMID:12098702 PMID:12387741 PMID:12479824

    Open questions at the time
    • Full catalog of activation vs. repression targets unknown
    • Mechanism of Notch1 repression (direct binding vs. indirect) not resolved
  6. 2003 High

    Separating chromatin accessibility from recombination competence at the IgH locus showed that Pax5 controls a mechanistic step in V(D)J recombination beyond simply opening chromatin.

    Evidence Pax5−/− pro-B cells showed normal histone acetylation and germline transcription at distal VH genes but failed to recombine them

    PMID:12514097

    Open questions at the time
    • The specific post-accessibility step controlled by Pax5 not identified
    • Whether locus contraction or RAG recruitment is the limiting step unknown
  7. 2004 High

    3D FISH demonstrated that PAX5 induces physical contraction of the IgH locus, explaining how distal VH gene segments are brought into recombination range.

    Evidence Pax5 reconstitution in Pax5−/− pro-B cells restored IgH locus contraction measured by 3D FISH and distal VH-DJH rearrangement

    PMID:15004008

    Open questions at the time
    • Molecular mechanism linking Pax5 to locus contraction unknown
    • Whether Pax5 acts directly on IgH locus architecture or via intermediate factors unclear
  8. 2006 High

    Physical interaction of PAX5 with the RAG1-RAG2 complex and enhancement of RAG cleavage at VH segments revealed a direct non-transcriptional mechanism by which PAX5 promotes V(D)J recombination.

    Evidence Co-immunoprecipitation of Pax5 with RAG1/RAG2, ChIP at VH genes, and in vitro RAG cleavage assay

    PMID:16680144

    Open questions at the time
    • Structural basis of Pax5-RAG interaction undefined
    • Relative contribution of RAG recruitment vs. locus contraction to distal VH recombination not quantified
  9. 2007 High

    Direct repression of PRDM1/Blimp1 by PAX5 established a mutual antagonism circuit controlling the B-cell versus plasma-cell fate decision.

    Evidence EMSA, ChIP at PRDM1 promoter, ectopic PAX5 expression, and PRDM1 promoter mutant reporters

    PMID:17682124

    Open questions at the time
    • Upstream signals that tip the Pax5-Blimp1 balance not fully characterized
    • Role of additional cofactors at the PRDM1 locus not explored
  10. 2009 High

    SWI/SNF recruitment was identified as the chromatin-remodeling mechanism through which PAX5 activates target genes, while Mi-2/NuRD opposes this at overlapping targets such as mb-1.

    Evidence Knockdown of SWI/SNF and NuRD subunits combined with inducible Pax5:ER, chromatin accessibility, and bisulfite sequencing

    PMID:19549820

    Open questions at the time
    • Direct physical interaction between Pax5 and SWI/SNF subunits not demonstrated
    • Genome-wide extent of SWI/SNF vs. NuRD antagonism at Pax5 targets not mapped
  11. 2012 High

    Genome-wide mapping revealed that PAX5 binds ~40% of cis-regulatory elements but functionally regulates only ~4% of bound genes, resolving the discrepancy between widespread binding and limited transcriptional output and showing stage-specific target gene programs.

    Evidence ChIP-seq, DNase I hypersensitivity, histone modification profiling, and RNA-seq in wild-type vs. Pax5−/− pro-B and mature B cells

    PMID:22669466

    Open questions at the time
    • Determinants distinguishing productive from non-productive binding events unresolved
    • Co-factor requirements at regulated vs. non-regulated sites not characterized
  12. 2020 High

    The mechanism of IgH locus contraction was solved: PAX5 represses Wapl via PRC2-mediated bivalent chromatin, extending cohesin residence time to drive loop extrusion across the IgH locus.

    Evidence ChIP-seq for Pax5/PRC2/H3K27me3, conditional Wapl KO, Hi-C, and cohesin ChIP-seq in pro-B cells

    PMID:32612238

    Open questions at the time
    • Whether Pax5-mediated Wapl repression operates at other recombining loci (e.g. Igκ, TCR) not tested
    • Quantitative relationship between Wapl levels and cohesin loop extrusion distance unknown
  13. 2021 High

    PAX5 sustains PI3K-AKT signaling in mature B cells by post-transcriptionally suppressing PTEN, revealing a non-transcriptional arm of PAX5 function required for B-cell proliferation upon antigen receptor stimulation.

    Evidence Conditional Pax5 deletion in mature B cells, PTEN/AKT Western blots, Pten/Pax5 double-mutant rescue

    PMID:34301800

    Open questions at the time
    • Identity of PAX5-regulated microRNAs targeting PTEN not established
    • Whether PTEN regulation is direct or via intermediate factors not resolved
  14. 2022 High

    PAX5 mutations were definitively established as B-ALL drivers: the recurrent P80R mutation impairs B-lymphoid development and leukemia enhancer regulation, including CD58 enhancer activation relevant to immunotherapy resistance.

    Evidence Knockin mouse models, genome-wide CRISPR screens, ChIP/ATAC-seq at CD58, blinatumomab killing assays

    PMID:30643249 PMID:35156727 PMID:36516256

    Open questions at the time
    • Full spectrum of enhancers dysregulated by P80R not cataloged
    • Whether P80R affects Pax5-RAG interaction or IgH contraction not tested
  15. 2024 High

    Acute in vivo degradation confirmed PAX5 functions predominantly as a transcriptional activator across B-cell development, directly inducing Rag1/Rag2/Dntt/Irf4/Irf8 and co-repressing Wapl with Ebf1.

    Evidence Auxin-inducible degron system in mice with RNA-seq, ATAC-seq, and ChIP-seq across pro-B, small pre-B, and immature B cells

    PMID:39179932

    Open questions at the time
    • Kinetics of target gene loss after acute Pax5 degradation not fully resolved for all stages
    • Whether Pax5 and Ebf1 cooperate at the same Wapl regulatory element or independent elements not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of PAX5 interactions with RAG and cohesin regulators, the identity of PAX5-regulated miRNAs controlling PTEN, and the rules distinguishing the ~4% of bound sites that are functionally regulated from the majority of inert binding events.
  • No crystal/cryo-EM structure of Pax5-RAG complex
  • Identity of Pax5-regulated Pten-targeting miRNAs unknown
  • Rules discriminating productive vs. non-productive Pax5 binding sites genome-wide not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-168256 Immune System 9 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-4839726 Chromatin organization 3
Partners
APEX1DAXXEBF1GRG4MYBRAG1RAG2

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 PAX5/BSAP directly binds to a high-affinity site in the CD19 promoter (at the -30 region in place of a TATA box), occupies this site in vivo in B cells but not plasma or HeLa cells, and is required for B-cell-specific transcriptional activation of CD19. In vitro protein-DNA binding, in vivo footprinting, transient transfection reporter assays Molecular and cellular biology High 1375324
2000 Pax5 exerts transcriptional repression by physically recruiting members of the Groucho corepressor family (e.g., Grg4). Interaction is mediated by the octapeptide motif and C-terminal transactivation domain of Pax5 and the N-terminal Q and central SP regions of Grg4. Phosphorylation state of Grg4 is altered upon Pax5 binding. Yeast two-hybrid screen, co-immunoprecipitation, transient transfection reporter assays, domain mapping The EMBO journal High 10811620
1999 Loss of Pax5 in committed pro-B cells allows them to reconstitute long-term T cell development in RAG2-deficient hosts, demonstrating that Pax5 is required for B lineage commitment and that B lineage commitment is not determined by DJ rearrangement or expression of E2A, EBF, lambda5, VpreB, Igalpha, Igbeta. Genetic loss-of-function (Pax5-/- mice), adoptive transfer into RAG2-/- recipients, in vivo reconstitution assay Nature High 10524629
2002 Conditional inactivation of Pax5 in committed pro-B cells causes them to regain multilineage potential, differentiating into macrophages in vitro and T cells in vivo, demonstrating that Pax5 is continuously required to maintain B lineage commitment. Conditional gene targeting (Cre-mediated excision), in vitro differentiation assay, in vivo reconstitution in RAG2-/- mice Science (New York, N.Y.) High 12098702
2002 Pax5 promotes B lymphopoiesis and blocks T cell development by repressing transcription of the T cell specification gene Notch1. Knockin mouse model with Pax5 expressed from Ikaros locus, gene expression analysis, loss-of-function phenotyping Immunity High 12479824
2004 Pax5 induces large-scale contraction of the IgH locus in pro-B cells, enabling distal VH-to-DJH rearrangements. Reconstitution of Pax5 in Pax5-/- pro-B cells induced locus contraction and distal VH-DJH rearrangements, while ectopic Pax5 in thymocytes promoted only proximal VH-DJH recombination. Genetic rescue experiments (Pax5 reconstitution in Pax5-/- pro-B cells), 3D FISH for locus contraction, V(D)J recombination analysis Genes & development High 15004008
2003 Pax5 is required for VH-to-DJH rearrangement; distal VH gene segments in Pax5-/- pro-B cells exhibit transcription and histone acetylation (chromatin accessibility) but fail to recombine, indicating Pax5 controls a recombination step distinct from chromatin accessibility. Analysis of Pax5-/- pro-B cells, histone acetylation assays, germline transcription analysis, V(D)J recombination frequency measurement Genes & development High 12514097
2002 Pax5 directly activates the BLNK gene, and BLNK expression is required for pre-BCR signaling (coupling Syk kinase to downstream effectors). Restoration of BLNK in Ig(mu) transgenic Pax5-/- pro-B cells reconstituted pre-BCR signaling and increased proliferation. Genetic rescue, retroviral complementation, signaling assays in Pax5-/- pro-B cells Immunity High 12387741
2006 Pax5 directly interacts with the RAG1-RAG2 complex via multiple Pax5 binding sites in VH gene coding regions, and this interaction enhances RAG-mediated VH recombination signal sequence cleavage in vitro. Co-immunoprecipitation of Pax5 with RAG1/RAG2 complex, ChIP (Pax5 occupancy at VH genes in B cells), in vitro RAG cleavage assay with VH substrate Nature immunology High 16680144
2009 SWI/SNF complexes (Brg1/Brm ATPases) are required for transcriptional activation by Pax5 and EBF, while Mi-2/NuRD (Mi-2beta subunit) opposes their action by restricting chromatin accessibility and DNA demethylation at Pax5/EBF target genes such as mb-1. Knockdown of SWI/SNF and Mi-2/NuRD subunits, tamoxifen-inducible EBF:ER and Pax5:ER fusion proteins, chromatin accessibility assays, bisulfite sequencing Proceedings of the National Academy of Sciences of the United States of America High 19549820
2012 Genome-wide analysis showed that Pax5 binds ~40% of cis-regulatory elements and ~8000 target genes in pro-B and mature B cells, but directly regulates only ~4% of bound genes by inducing enhancers at activated targets and eliminating DNase I hypersensitive sites at repressed targets. Regulated target genes differ substantially between pro-B and mature B cells. Genome-wide ChIP-seq, DNase I hypersensitive site mapping, histone modification profiling, RNA-seq in WT vs. Pax5-/- cells The EMBO journal High 22669466
2020 Pax5 represses the cohesin-release factor Wapl gene (via a single Pax5-binding site by recruiting Polycomb Repressive Complex 2 to induce bivalent chromatin at the Wapl promoter) in pro-B and pre-B cells, thereby extending cohesin residence on chromatin and enabling loop extrusion-driven IgH locus contraction and VH-to-DJH recombination. ChIP-seq (Pax5 binding, PRC2/H3K27me3, H3K4me3), conditional Wapl KO, Hi-C/chromosome conformation capture, cohesin ChIP-seq, Pax5 mutant analysis Nature High 32612238
2002 Pax5 interacts with the coactivator Daxx via the partial homeodomain of Pax5 and the C-terminal fragment of Daxx. In B cells, this interaction can result in both transcriptional corepression and coactivation, and involves recruitment of CBP (CREB binding protein) to Pax5-Daxx complexes. Yeast two-hybrid, co-immunoprecipitation, transient transfection reporter assays, domain mapping in 293T and B cell lines The Journal of biological chemistry Medium 11799127
1996 BSAP/Pax5 represses the J chain gene by binding to a negative regulatory motif in its promoter; this repression is relieved during antigen-driven stages by IL-2-induced down-regulation of BSAP RNA, demonstrating concentration-dependent repressor vs. activator switching. Transcriptional reporter assays, BSAP overexpression in plasma cells, IL-2 stimulation and antisense experiments Immunity Medium 8885870
1998 BSAP/Pax5 activator motifs have ~20-fold higher binding affinity than repressor motifs, and the context of the binding motif (not affinity alone) determines whether BSAP acts as an activator or repressor. In vitro DNA binding affinity measurements, exchange of activator/repressor binding motifs, reporter assays Science (New York, N.Y.) Medium 9506950
1995 Pax5/BSAP regulates the immunoglobulin heavy chain 3' alpha enhancer by suppressing binding of the Ets family protein NF-alphaP, which is required for maximal enhancer activity; blocking Pax5 binding in vivo with a triple-helix-forming oligonucleotide revealed an alpha-P site footprint and increased IgH transcription. In vitro binding assays, in vivo footprinting, triple-helix oligonucleotide blockade, transfection reporter assays Proceedings of the National Academy of Sciences of the United States of America High 7777508
2000 Oxidative stress triggers translocation of Ref-1/APE from the cytoplasm to the nucleus in B lymphocytes, where Ref-1 directly interacts with BSAP/Pax5 and enhances its DNA-binding activity; this results in increased BSAP/Pax5-dependent transcription from the CD19 promoter. Western blot of nuclear fractions, EMSA, in situ immunocytochemistry pulse-chase, co-transfection reporter assays Nucleic acids research Medium 10666449
2003 CD40 cross-linking in B cells triggers APE/Ref-1 nuclear translocation, which then modulates the DNA-binding activity of both Pax5a/BSAP and EBF. Pax5a physically interacts with EBF and enhances EBF DNA-binding activity, and together they cooperatively activate the blk promoter. Subcellular fractionation, EMSA, co-immunoprecipitation, luciferase reporter assays The Journal of biological chemistry Medium 14594818
2002 Pax5 activates transcription of the RAG-2 promoter cooperatively with c-Myb through synergistic DNA binding; the C-terminus of c-Myb mediates interaction with Pax5, and dominant-negative c-Myb suppresses RAG-2 promoter activity in pre-B cells. EMSA, transfection reporter assays, deletion mapping, dominant-negative experiments in pre-B cell lines Blood Medium 11781241
2006 Pax5 is required for kappa sterile transcription at the Igkappa locus and for subsequent Igkappa gene rearrangement. In Pax5-deficient pre-BI cells the Jkappa locus localizes to the nuclear periphery (repressive compartment), and the transactivation domain of Pax5 is specifically required for kappa sterile transcription. Pax5-/- pre-BI cell lines, in vitro kappa rearrangement assay, FISH (nuclear positioning), transfection of Pax5 domain mutants Journal of immunology (Baltimore, Md. : 1950) High 15067064
2006 Loss of Pax5 in a DT40 B cell line leads to loss of BCR signaling, upregulation of plasma cell transcription factors Blimp-1 and XBP-1, downregulation of Bcl-6, and elevated IgM secretion, demonstrating that Pax5 actively inhibits plasma cell differentiation. Conditional gene targeting in DT40 cells (Pax5-/-), flow cytometry, gene expression analysis, rescue by Pax5 re-expression Immunity High 16546097
2007 BSAP/Pax5 binds to the EBV Wp promoter in transformed B cells (confirmed by ChIP) and is required for B-cell-specific activity of Wp; mutation of Pax5 binding sites in Wp abolishes early viral transcription, latent protein expression, and B cell transformation without affecting epithelial cell infection. Chromatin immunoprecipitation (ChIP), recombinant EBV mutants with Pax5-binding site mutations, functional infection assays Journal of virology High 17626071
2009 PAX5 directly activates c-Met transcription in small cell lung cancer cells, binds to the c-Met promoter (confirmed by ChIP), and phospho-c-Met co-localizes and interacts with PAX5 in the nucleus of HGF-treated SCLC cells. Luciferase reporter assay, ChIP, co-immunoprecipitation, PAX5 knockdown Laboratory investigation; a journal of technical methods and pathology Medium 19139719
2007 MTA1 (when acetylated at Lys626) interacts with p300 histone acetyltransferase and is recruited to the Pax5 promoter to stimulate Pax5 transcription, identified by ChIP assay. Chromatin immunoprecipitation, co-immunoprecipitation, gene expression profiling Cancer research Medium 17671180
2007 BSAP/Pax5 represses BLIMP1/PRDM1 transcription by binding to a BSAP site in the PRDM1 promoter (confirmed by EMSA and ChIP in vivo), forming a mutual antagonism feedback loop between Pax5 and Blimp1. EMSA, ChIP, ectopic BSAP expression, PRDM1 promoter mutant reporter assays Blood High 17682124
2010 PAX5 activates hTERT transcription in B cells by binding to sites downstream of the ATG start site (confirmed by EMSA and ChIP); PAX5 knockdown represses hTERT transcription, and ectopic PAX5 expression in telomerase-negative fibroblasts is sufficient to activate hTERT. EMSA, ChIP, siRNA knockdown, ectopic expression in fibroblasts The Journal of pathology Medium 19806612
2014 The PAX5-JAK2 fusion protein localizes to the nucleus, binds wild-type PAX5 target loci (via PAX5 paired domain), and functions as a constitutively active nuclear kinase that autophosphorylates and phosphorylates/activates STAT proteins in a non-canonical manner, enabling cytokine-independent growth. Subcellular fractionation/immunofluorescence, ChIP, kinase assays, STAT phosphorylation assays, Ba/F3 cytokine-independent growth assay Blood High 25515960
2022 PAX5-JAK2 drives B-ALL as a dual-hit through PAX5 DNA-binding (requiring loss of the WT Pax5 allele for efficient chromatin binding) and constitutive nuclear JAK2 kinase activity that phosphorylates STAT5 within the nucleus, increasing STAT5 target gene expression. Knockin mouse model (Pax5Jak2/+), ChIP, phospho-STAT5 immunostaining, gene expression profiling, kinase domain mutagenesis The EMBO journal High 35156727
2011 PAX5-ETV6 and other PAX5 fusion proteins with multimerization domains bind PAX5 target chromatin with increased stability (demonstrated by FRAP), acting as dominant-negative inhibitors by competing with wild-type PAX5 for target-site binding; this requires multimerization rather than the C-terminal repressor-binding domains. FRAP in living cells, in vitro DNA binding assays, mutagenesis of multimerization domain, reporter assays Oncogene High 21765475
2011 PAX5-PML functions as a dominant-negative inhibitor of both PAX5 and PML. PAX5-PML lacks direct DNA-binding activity despite retaining the DNA-binding domain, but binds PAX5 target promoters by associating with endogenous PAX5 (shown by ChIP). It also disrupts PML nuclear bodies and inhibits PML sumoylation, conferring apoptosis resistance. Luciferase reporter assay, ChIP, in vitro DNA binding assay, immunofluorescence of PML nuclear bodies, Co-IP Oncogene High 21217775
2017 PAX5-ETV6 arrests B-lymphopoiesis at the pro-B to pre-B transition and, contrary to the proposed dominant-negative model, does not broadly interfere with regulated Pax5 target gene expression; PAX5-ETV6 cooperates with Cdkn2a/b loss to promote B-ALL, regulating genes involved in pre-BCR signaling and migration/adhesion. Knockin mouse model, RNA-seq, ChIP-seq, tumor development analysis The EMBO journal High 28219927
2021 Conditional loss of Pax5 in peripheral B cells impairs PI3K-AKT signaling due to increased PTEN protein expression (post-transcriptional regulation, likely through Pten-targeting microRNAs), resulting in failure to proliferate upon BCR or TLR stimulation. Conditional Pax5 mutagenesis in mature B cells, Western blot of PTEN, AKT phosphorylation assays, Pten/Pax5 double-mutant rescue experiment Science immunology High 34301800
2022 PAX5 epigenetically activates a CD58 enhancer; the PAX5 P80R leukemia mutation disrupts this enhancer, reducing CD58 expression and thereby impairing blinatumomab-induced T cell activation. Genome-wide CRISPR screen, transcription factor CRISPR screen, ChIP/ATAC-seq at CD58 locus, genome editing of PAX5 P80R, functional blinatumomab killing assay Science advances High 36516256
2024 Acute in vivo protein degradation of Pax5 revealed it functions predominantly as a transcriptional activator by inducing open chromatin at target genes in pro-B, small pre-B, and immature B cells. Pax5 directly activates Rag1, Rag2, Dntt, Irf4, and Irf8 to control V(D)J recombination, and like Ebf1, represses Wapl to promote Igh loop extrusion. Auxin-inducible degron (acute protein degradation in mice), RNA-seq, ATAC-seq, ChIP-seq across three B cell developmental stages Nature immunology High 39179932
1994 BSAP/Pax5 binds to the LPS/IL-4-responsive Iepsilon promoter and is essential for LPS/IL-4-induced germ-line epsilon transcription; a BSAP binding site can functionally substitute for the native epsilon-associated site (epsilon-foot) in reporter assays. EMSA, transient transfection reporter assays in M12.4.1 B cell line Journal of immunology (Baltimore, Md. : 1950) Medium 8144891
2010 In t(8;21) AML cells, PAX5 expression is sufficient to activate CD19 transcription: PAX5 binds the CD19 promoter and enhancer (shown by ChIP), remodels chromatin at the promoter, and exploits a pre-existing poised chromatin configuration at CD19 in myeloid progenitors. ChIP at CD19 locus, chromatin accessibility assays, correlation of PAX5 and CD19 expression in t(8;21) AML cells Oncogene Medium 20208555
2019 The PAX5 p.Pro80Arg mutation impairs B lymphoid development and, when combined with biallelic PAX5 alteration, promotes B-ALL development in vivo, establishing the mutation as a driver of leukemogenesis. Knockin mouse model expressing PAX5 p.Pro80Arg, in vivo B-ALL development assay, gene expression analysis Nature genetics High 30643249
2002 DNA methylation is the dominant mechanism of Pax5 silencing in terminally differentiated plasma cells: CpG sites in the TATA-containing upstream promoter are fully methylated in myeloma lines; demethylation with 5-aza-dC restores Pax5 expression and activates CD19 and mb-1 target genes. The downstream promoter is silenced by histone deacetylation. Bisulfite sequencing, 5-aza-dC and trichostatin A treatment, RT-PCR for Pax5 and target genes Molecular immunology Medium 12044782
2022 PAX5 overexpression in pancreatic beta cells causes severe mitochondrial dysfunction and impairs insulin secretion, identifying a role for Pax5 in regulating beta cell metabolic function. Overexpression in human islets/beta cells, insulin secretion assay, mitochondrial function assays, mouse KO metabolic phenotyping The Journal of clinical investigation Medium 36656641

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Pax5: the guardian of B cell identity and function. Nature immunology 506 17440452
2019 PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia. Nature genetics 464 30643249
2004 Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Genes & development 324 15004008
1992 The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP. Molecular and cellular biology 296 1375324
1999 Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors. Nature 277 10524629
2013 A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nature genetics 242 24013638
2002 Reversion of B cell commitment upon loss of Pax5 expression. Science (New York, N.Y.) 225 12098702
2000 Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family. The EMBO journal 211 10811620
2008 Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Nature immunology 200 18176567
2011 Pax5: a master regulator of B cell development and leukemogenesis. Advances in immunology 190 21970955
2012 The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis. The EMBO journal 184 22669466
1999 Role of Pax-5 in the regulation of a mid-hindbrain organizer's activity. Development, growth & differentiation 184 10445503
2002 Pax5 promotes B lymphopoiesis and blocks T cell development by repressing Notch1. Immunity 180 12479824
2006 Loss of Pax5 promotes plasma cell differentiation. Immunity 169 16546097
1996 The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene. Blood 151 8943844
1997 Cooperation of Pax2 and Pax5 in midbrain and cerebellum development. Proceedings of the National Academy of Sciences of the United States of America 143 9159136
2011 Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia. The Journal of experimental medicine 135 21606506
1994 The B cell-specific transcription factor BSAP regulates B cell proliferation. The Journal of experimental medicine 132 7511679
2003 Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments. Genes & development 125 12514097
2002 Control of pre-BCR signaling by Pax5-dependent activation of the BLNK gene. Immunity 121 12387741
1995 Deregulated expression of PAX5 in medulloblastoma. Proceedings of the National Academy of Sciences of the United States of America 119 7777574
2009 Opposing effects of SWI/SNF and Mi-2/NuRD chromatin remodeling complexes on epigenetic reprogramming by EBF and Pax5. Proceedings of the National Academy of Sciences of the United States of America 114 19549820
1999 Independent regulation of the two Pax5 alleles during B-cell development. Nature genetics 113 10192389
2008 Identification of Pax5 target genes in early B cell differentiation. Journal of immunology (Baltimore, Md. : 1950) 110 18209069
2020 Wapl repression by Pax5 promotes V gene recombination by Igh loop extrusion. Nature 106 32612238
2019 LncRNA FOXP4-AS1 is activated by PAX5 and promotes the growth of prostate cancer by sequestering miR-3184-5p to upregulate FOXP4. Cell death & disease 103 31209207
2002 The interaction of Pax5 (BSAP) with Daxx can result in transcriptional activation in B cells. The Journal of biological chemistry 97 11799127
1996 An interleukin-2 signal relieves BSAP (Pax5)-mediated repression of the immunoglobulin J chain gene. Immunity 94 8885870
2009 PAX5 is expressed in small-cell lung cancer and positively regulates c-Met transcription. Laboratory investigation; a journal of technical methods and pathology 90 19139719
2000 An 'environment to nucleus' signaling system operates in B lymphocytes: redox status modulates BSAP/Pax-5 activation through Ref-1 nuclear translocation. Nucleic acids research 87 10666449
2004 PAX5 expression in acute leukemias: higher B-lineage specificity than CD79a and selective association with t(8;21)-acute myelogenous leukemia. Cancer research 83 15492262
1995 Pax5 (BSAP) regulates the murine immunoglobulin 3' alpha enhancer by suppressing binding of NF-alpha P, a protein that controls heavy chain transcription. Proceedings of the National Academy of Sciences of the United States of America 83 7777508
1998 Deregulated PAX-5 transcription from a translocated IgH promoter in marginal zone lymphoma. Blood 72 9808580
2002 Multiple hematopoietic cell lineages develop in vivo from transplanted Pax5-deficient pre-B I-cell clones. Blood 70 11781227
1995 The role of BSAP (Pax-5) in B-cell development. Current opinion in genetics & development 67 8664547
2007 Identification of Pax5 as a target of MTA1 in B-cell lymphomas. Cancer research 60 17671180
2006 Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes. Nature immunology 60 16680144
1994 The transcription factor BSAP (NF-HB) is essential for immunoglobulin germ-line epsilon transcription. Journal of immunology (Baltimore, Md. : 1950) 56 8144891
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