Affinage

BCL11B

B-cell lymphoma/leukemia 11B · UniProt Q9C0K0

Length
894 aa
Mass
95.5 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCL11B (CTIP2) is a C2H2/CCHC zinc finger transcription factor that serves as a master regulator of cell identity across multiple lineages, including T lymphocytes, innate lymphoid cells, cortical and striatal neurons, olfactory sensory neurons, keratinocytes, and ameloblasts. It functions as both a transcriptional repressor and activator in a context-dependent manner: as a repressor, it recruits the NuRD chromatin-remodeling complex, HDAC1/2, SUV39H1, and LSD1 to silence targets such as HIV-1, p21WAF1, TSLP, and Id2 through heterochromatin establishment (PMID:17245431, PMID:16950772, PMID:19581932); as an activator, it directly binds and sustains expression of lineage-critical genes including Foxp3, Gfi1, EGFR, and Notch1, and cooperates with RUNX1 to recruit mSWI/SNF complexes to poise T cell effector loci (PMID:21875956, PMID:26231117, PMID:38632339). BCL11B homodimerizes through its N-terminal CCHC zinc finger—a requirement for transcriptional activity—and its genomic occupancy, post-translational modifications, and protein complex composition differ between cell types, enabling it to control distinct gene programs in pro-T cells versus ILC2s (PMID:29203643, PMID:31653691). De novo BCL11B mutations cause human immunodeficiency with arrested T-cell development and impaired hematopoietic progenitor migration (PMID:27959755).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 High

    Early work established that BCL11B is essential for T-cell development and identified its role as a heterochromatin organizer: Bcl11b knockout mice revealed a block at the DN stage with failed V(D)J recombination, while domain mapping showed BCL11B sequesters HIV-1 Tat into HP1α-containing heterochromatic structures to silence viral transcription.

    Evidence Bcl11b germline knockout with recombination PCR and flow cytometry; co-IP/confocal with deletion mutants in transfected cells

    PMID:12692243 PMID:12717433

    Open questions at the time
    • Mechanism by which BCL11B controls V(D)J recombination accessibility was not defined
    • Whether HP1α interaction is required for endogenous gene silencing beyond HIV-1 was untested
  2. 2007 High

    The chromatin-modifying machinery through which BCL11B silences genes was delineated: BCL11B recruits HDAC1/2 and SUV39H1 to the HIV-1 promoter to establish H3 deacetylation and H3K9 trimethylation, and a parallel study linked BCL11B to Sirt1 and the DNA replication stress response through Chk1 phosphorylation.

    Evidence ChIP, co-IP, and pharmacological inhibition in microglial cells; siRNA knockdown with Sirt1 co-IP and Chk1 phosphorylation assay in T-cell lines

    PMID:17245431 PMID:17369851

    Open questions at the time
    • Whether HDAC1/2 and SUV39H1 are recruited as a single complex or sequentially was unresolved
    • Sirt1–BCL11B interaction lacked independent replication
  3. 2006 High

    BCL11B was shown to physically associate with the NuRD complex through direct binding to RbAp46/48, establishing NuRD as a major effector of BCL11B-mediated transcriptional repression at endogenous gene promoters such as p57KIP2.

    Evidence Co-IP, in vitro pulldown, and ChIP co-occupancy at the p57KIP2 promoter in neuroblastoma cells

    PMID:16950772

    Open questions at the time
    • Full stoichiometry and subunit composition of the BCL11B–NuRD complex were not determined
    • Whether NuRD mediates all BCL11B repressive functions or only a subset was unclear
  4. 2008 High

    BCL11B's roles in neuronal fate specification were established: it acts downstream of Fezf2 to direct subcortical axon projections of corticospinal neurons, and is required for medium spiny neuron differentiation and striatal patch organization.

    Evidence Epistasis analysis with in utero electroporation and axon tracing in Fezf2-KO rescue; Ctip2 knockout with immunohistochemistry and in situ hybridization for MSN markers

    PMID:18199763 PMID:18678899

    Open questions at the time
    • Direct transcriptional targets mediating axon guidance decisions were not identified
    • Whether BCL11B acts through NuRD or distinct complexes in neurons was unknown
  5. 2010 High

    BCL11B was identified as the gatekeeper of T-cell versus NK-cell identity: its deletion in committed T cells reprograms them into functional NK-like cells, and it acts at the DN2-to-DN3 transition to repress NK-associated and stem cell genes, while also directly binding CD8 enhancers to control effector T-cell function.

    Evidence Conditional and germline Bcl11b knockouts with gene expression profiling, cytotoxicity assays, in vivo tumor and viral infection models, ChIP at CD8 enhancers

    PMID:20538915 PMID:20595614 PMID:20660613

    Open questions at the time
    • Whether T-to-NK reprogramming occurs through a multipotent intermediate was unresolved
    • The complete set of BCL11B-repressed NK genes was not defined genome-wide
  6. 2011 High

    BCL11B's direct transcriptional targets were expanded to include Foxp3 and IL-10 in Tregs, lysosomal genes controlling iNKT cell selection, and neurotrophin pathway components in the striatum, while LSD1 was identified as an additional BCL11B-cooperating chromatin modifier at the HIV-1 promoter.

    Evidence ChIP with promoter mutagenesis in Tregs; conditional KO with electron microscopy and lipid analysis for iNKT; ChIP-seq with expression profiling in striatal cells; ChIP/co-IP for LSD1 at HIV-1 promoter

    PMID:21444811 PMID:21875956 PMID:21912641 PMID:22067449

    Open questions at the time
    • How BCL11B switches from repressor to activator at Foxp3 was mechanistically unexplained
    • LSD1 cooperation was characterized at HIV-1 but not validated at endogenous targets
  7. 2012 High

    BCL11B's functions were extended to epithelial biology and hippocampal neurogenesis: it directly activates EGFR and Notch1 in keratinocytes, regulates sphingolipid biosynthesis genes in skin, represses TSLP to prevent atopic dermatitis, and controls dentate gyrus neurogenesis through Desmoplakin as a direct target.

    Evidence ChIP at EGFR/Notch1/TSLP/sphingolipid promoters; conditional epidermal and forebrain KO models; rescue of neurogenesis by Desmoplakin re-expression; lipidomics

    PMID:22588081 PMID:23015591 PMID:23096701 PMID:23284675

    Open questions at the time
    • How calcium-induced SUMOylation and proteasomal degradation of BCL11B are coordinated in vivo was not fully resolved
    • Whether sphingolipid changes are a primary or secondary consequence of BCL11B loss was unclear
  8. 2013 High

    A kinase-independent function was revealed: BCL11B directly interacts with HEXIM1 and the 7SK snRNP to sequester P-TEFb, repressing CDK9 kinase activity at target promoters including MYH7 in cardiomyopathic hearts, while a distal enhancer (~850 kb downstream) was identified as the T-cell-specific regulatory element that activates BCL11B expression through chromatin looping.

    Evidence In vitro CDK9 kinase assay, co-purification and ChIP in cardiac cells; BAC transgenics and chromatin looping assays for enhancer

    PMID:23741008 PMID:23852730

    Open questions at the time
    • Whether P-TEFb sequestration is a general mechanism at all BCL11B-repressed promoters was untested
    • Factors controlling enhancer–promoter loop formation beyond TCF-1 were not fully defined
  9. 2016 High

    The upstream regulatory logic activating BCL11B expression during T-cell commitment was decoded: four inputs (TCF-1, GATA-3, Notch, Runx1) converge on the distal enhancer with distinct kinetics—poising, stochastic permissivity, and amplitude control—resolving how BCL11B activation timing is regulated.

    Evidence Bcl11b knock-in fluorescent reporter with single-cell live imaging; systematic genetic deletion of each factor

    PMID:27376470

    Open questions at the time
    • Epigenetic state transitions at the enhancer during each regulatory input were not fully mapped
    • Whether the same regulatory logic operates in non-T lineages expressing BCL11B was unknown
  10. 2016 High

    A de novo BCL11B missense mutation (N441K) was shown to cause human immunodeficiency by acting as a dominant-negative that abrogates DNA binding and arrests T-cell development, also revealing a previously unappreciated prethymic role for BCL11B in hematopoietic progenitor migration.

    Evidence Exome sequencing of patient; zebrafish bcl11ba KO rescue with WT versus mutant human BCL11B; human HSC migration assays

    PMID:27959755

    Open questions at the time
    • The molecular mechanism of prethymic migration control was not defined
    • Whether other BCL11B mutations cause the same syndrome was not yet established
  11. 2018 High

    BCL11B's oligomeric state was resolved: it homodimerizes through the N-terminal CCHC zinc finger, and this dimerization is necessary for transcriptional activity, cell cycle arrest, and protection from DNA damage; the N441K pathogenic mutation acts by forming nonfunctional dimers with wild-type protein.

    Evidence FACS-FRET, AP-MS, CCHC zinc finger mutagenesis, cell cycle and apoptosis assays

    PMID:29203643

    Open questions at the time
    • Whether BCL11B can also heterodimerize with BCL11A was not addressed
    • Structural basis of the dimer interface at atomic resolution was lacking
  12. 2018 High

    BCL11B's interaction with GATA3 was characterized as a direct protein–protein association at co-occupied Th2 cis-regulatory elements, where BCL11B restrains GATA3-driven type 2 cytokine overproduction and maintains chromatin accessibility at cytokine loci while silencing the Il4 HS IV element through Runx3 restriction.

    Evidence Co-IP, ChIP-seq, ATAC-seq, RNA-seq, conditional KO in Th2 cells, helminth infection model

    PMID:29514917 PMID:29700302

    Open questions at the time
    • Structural basis of BCL11B–GATA3 interaction was undetermined
    • Whether this restraining mechanism operates in human Th2-driven disease was untested in vivo
  13. 2019 High

    Context-dependent BCL11B function was mechanistically explained: ChIP-seq in pro-T cells versus ILC2s showed largely non-overlapping genomic binding, with distinct post-translational modifications and partner complexes in each lineage; simultaneously, BCL11B was shown to determine odorant receptor class choice in olfactory neurons and regulate PKA signaling in human striatal neurons.

    Evidence ChIP-seq and MS of BCL11B complexes in two lineages with conditional KO; OSN-specific KO/overexpression with enhancer reporters; CTIP2-deficient hPSC-derived MSNs with phosphoprotein analysis

    PMID:31396576 PMID:31447328 PMID:31653691

    Open questions at the time
    • Specific PTMs driving cell-type-specific binding were not fully catalogued
    • Whether BCL11B directly regulates PKA pathway genes or acts indirectly through DARPP-32 was unclear
  14. 2019 Medium

    HIV-1 Vpr was found to counteract BCL11B-mediated latency by targeting CTIP2 for proteasomal degradation via the Cul4A–DDB1–DCAF1 ubiquitin ligase complex, revealing a viral strategy to reactivate latent provirus by eliminating its silencing factor.

    Evidence Co-IP, proteasome inhibitor rescue, ChIP at latent HIV-1 promoter, siRNA/dominant-negative in microglial latency model

    PMID:31511615

    Open questions at the time
    • Whether Vpr-mediated BCL11B degradation occurs in primary latently infected CD4+ T cells in vivo was not demonstrated
    • Quantitative contribution of BCL11B degradation versus other Vpr targets to latency reversal was unresolved
  15. 2024 High

    BCL11B was shown to participate in a transcription factor relay with PU.1 during T lineage commitment: as PU.1 is silenced, BCL11B together with RUNX1 takes over mSWI/SNF complex recruitment at T effector loci, maintaining chromatin accessibility and poising the effector gene program early in development.

    Evidence ChIP-seq and ATAC-seq with conditional KO of PU.1 and BCL11B; mSWI/SNF co-immunoprecipitation

    PMID:38632339

    Open questions at the time
    • Whether BCL11B is a stable mSWI/SNF subunit or a transient recruiter was not resolved
    • How BCL11B discriminates between mSWI/SNF-dependent and NuRD-dependent targets at the same developmental stage is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of BCL11B homodimerization and partner interactions; how post-translational modifications switch BCL11B between activator and repressor modes; and the full spectrum of human disease caused by BCL11B mutations beyond the initial immunodeficiency case.
  • No high-resolution structure of BCL11B or its complexes exists
  • Systematic mapping of PTMs to functional outputs across cell types is lacking
  • Genotype–phenotype relationships for BCL11B variants in neurodevelopmental and immune disorders are incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 4 GO:0042393 histone binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 5 GO:0005654 nucleoplasm 3 GO:0005694 chromosome 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-168256 Immune System 7 R-HSA-1266738 Developmental Biology 4 R-HSA-4839726 Chromatin organization 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3
Partners
GATA3HDAC1HDAC2HEXIM1HP1ARBBP7RUNX1SUV39H1
Complex memberships
7SK/HEXIM1/P-TEFb snRNPNuRDmSWI/SNF

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CTIP2/BCL11B recruits histone deacetylases HDAC1 and HDAC2 to the HIV-1 promoter to promote local histone H3 deacetylation, and associates with histone methyltransferase SUV39H1 to increase H3K9 methylation, enabling HP1 protein recruitment and heterochromatin formation that silences HIV-1 transcription in microglial cells. ChIP, co-IP, transfection/reporter assays, pharmacological inhibition The EMBO journal High 17245431
2003 CTIP2/BCL11B interacts with HP1α and HIV-1 Tat protein to form a three-protein complex, relocalizing Tat into CTIP2-induced nuclear heterochromatic structures via two distinct CTIP2 domains (aa 145-434 interacting with Tat N-terminus; aa 717-813 interacting with HP1), thereby inhibiting Tat-mediated HIV-1 transactivation. Co-IP, confocal microscopy, deletion mutagenesis, reporter assays Journal of virology High 12692243
2006 CTIP2/BCL11B associates with the NuRD chromatin-remodeling/deacetylase complex through direct interaction with RbAp46 and RbAp48; NuRD components are recruited to a promoter template in a CTIP2-dependent manner, and both CTIP2 and NuRD co-occupy the p57KIP2 promoter to repress its transcription. Co-IP, pulldown, ChIP, reporter assays in SK-N-MC neuroblastoma cells The Journal of biological chemistry High 16950772
2009 CTIP2/BCL11B and SUV39H1 are co-recruited to the p21WAF1 gene promoter, where CTIP2 cooperates with SUV39H1 to promote H3K9 trimethylation and silence p21 transcription; chaetocin (SUV39H1 inhibitor) treatment relieves this repression. ChIP, siRNA knockdown, pharmacological inhibition, reporter assays Oncogene High 19581932
2013 CTIP2/BCL11B is a negative regulator of P-TEFb: it copurifies and directly interacts with HEXIM1 and, via the 7SK snRNA loop 2, with P-TEFb to form an inactive complex, significantly repressing CDK9 kinase activity and thereby suppressing P-TEFb-sensitive gene expression including at the MYH7 promoter in cardiomyopathic hearts. Co-purification, co-IP, in vitro CDK9 kinase assay, ChIP, siRNA knockdown, genome-wide transcriptomics Proceedings of the National Academy of Sciences of the United States of America High 23852730
2010 BCL11B is required for T lineage commitment in mice; it specifically represses natural killer cell-associated genes and downregulates stem/progenitor cell genes at the DN2-to-DN3 transition stage. Bcl11b knockout mouse model, gene expression profiling, flow cytometry Science (New York, N.Y.) High 20595614
2010 Deletion of Bcl11b in T cells causes them to acquire NK cell properties (morphologically and genetically similar to conventional NK cells) with retained tumor-killing capacity, demonstrating Bcl11b is required to maintain T cell identity and suppress NK cell programming. Conditional Bcl11b knockout, gene expression profiling, functional cytotoxicity assays, in vivo tumor metastasis model Science (New York, N.Y.) High 20538915
2003 Bcl11b is required for Tcrb V(D)J recombination (specifically Vβ-to-Dβ joining), pre-TCR complex surface expression, and thymocyte survival; Bcl11b-deficient mice are blocked at the CD4−CD8− double-negative stage with profound thymic apoptosis. Bcl11b knockout mouse model, flow cytometry, PCR-based recombination assay, Northern blot Nature immunology High 12717433
2007 BCL11B controls positive selection of both CD4 and CD8 thymocytes by maintaining proximal TCR signaling components; BCL11B-deficient DP thymocytes show impaired ERK phosphorylation and calcium flux, and increased spontaneous apoptosis associated with elevated caspase-3 cleavage and altered pro-/anti-apoptotic factor balance, only partially rescued by BCL2 transgene. Conditional knockout, flow cytometry, calcium flux assay, ERK phosphorylation assay, transgenic TCR rescue experiments, apoptosis assays The Journal of experimental medicine High 17998389
2008 Ctip2/BCL11B acts downstream of Fezf2 to regulate subcortical axon projection fate in the cerebral cortex; ectopic Ctip2 expression redirects callosal neurons to project subcortically and rescues the axonal phenotype of Fezf2 knockout mice. Knockout mice, in utero electroporation, axon tracing, epistasis analysis Proceedings of the National Academy of Sciences of the United States of America High 18678899
2008 Ctip2/BCL11B is required for medium spiny neuron (MSN) differentiation and striatal architecture; Ctip2-null mice show dramatically reduced expression of MSN markers (DARPP-32, FOXP1, Chrm4, Reelin, MOR1, GluR1, Plexin-D1), failure of MSN patch aggregation, and abnormal dopaminergic innervation. Ctip2 knockout mouse model, immunohistochemistry, in situ hybridization, gene expression analysis The Journal of neuroscience : the official journal of the Society for Neuroscience High 18199763
2016 Bcl11b expression is activated by an asynchronous combination of four regulatory inputs: TCF-1 and GATA-3 provide early locus 'poising', Notch signaling provides stochastic permissivity, and Runx1 controls amplitude; these act via a far downstream enhancer (Major Peak, ~850 kb from the Bcl11b promoter) that loops to interact with the promoter. Bcl11b knock-in fluorescent reporter mice, single-cell live imaging, genetic deletion of transcription factors, looping/enhancer assays Nature immunology High 27376470
2013 A 1.9-kb enhancer element ('Major Peak') located ~850 kb downstream of Bcl11b is required for T-cell-specific Bcl11b expression; it contains TCF-1 binding sites and a conserved element needed for T-lineage activation and silencing in non-T cells, and physically loops to interact with the Bcl11b promoter-proximal region. Stable reporter assays, bacterial artificial chromosome transgenics, chromatin looping assays, deletion mutagenesis Blood High 23741008
2011 LSD1 histone demethylase cooperates with CTIP2 to repress HIV-1 transcription; LSD1 is recruited to the HIV-1 proximal promoter where its activity is associated with H3K4me3 and H3K9me3 epigenetic marks, and LSD1-induced H3K4 trimethylation is linked to hSET1 recruitment. ChIP, siRNA knockdown, reporter assays, co-IP Nucleic acids research Medium 22067449
2014 HMGA1 recruits the CTIP2-repressed inactive P-TEFb/7SK snRNP complex to cellular gene promoters and the HIV-1 promoter; knockdown of HMGA1 reduces ChIP signal for CTIP2/7SK/P-TEFb at these promoters, and CTIP2 and HMGA1 act synergistically to repress P-TEFb-dependent gene expression. ChIP, siRNA dual knockdown, reporter assays, co-IP Nucleic acids research Medium 24623795
2012 Bcl11b/Ctip2 regulates hippocampal dentate gyrus postnatal neurogenesis through a dual mechanism: feedback control of the progenitor cell compartment and regulation of granule cell differentiation; Desmoplakin is identified as a direct transcriptional target of Bcl11b, and re-expression of Desmoplakin in Bcl11b mutants rescues impaired neurogenesis. Forebrain-specific conditional knockout, ChIP (direct target validation), rescue experiments, behavioral testing The EMBO journal High 22588081
2011 Bcl11b directly binds to Foxp3 and IL-10 gene promoters and conserved noncoding sequences; mutation of the Bcl11b binding site in the Foxp3 promoter reduces reporter expression, demonstrating Bcl11b directly activates Foxp3 and IL-10 transcription in T regulatory cells. ChIP, promoter mutation/reporter assay, conditional knockout The Journal of experimental medicine High 21875956
2011 BCL11B structural mutations in T-ALL disrupt zinc finger domain structure required for DNA binding, as revealed by structural homology modeling; missense mutations in zinc finger domains abrogate the protein's DNA-binding capacity. Structural homology modeling, DNA copy number analysis, sequencing of patient specimens Blood Medium 21878675
2018 BCL11B homodimerizes through its N-terminal CCHC zinc finger motif; this dimerization is necessary and sufficient for transcriptional regulatory activity, cell cycle arrest induction, and protection against DNA damage-driven apoptosis. The pathogenic N441K dominant-negative mutation acts by forming a nonfunctional dimer with wild-type BCL11B. FACS-FRET assay, affinity purification/mass spectrometry, CCHC zinc finger mutagenesis, cell cycle analysis, apoptosis assay Molecular and cellular biology High 29203643
2016 A patient de novo missense mutation p.N441K in BCL11B produces a dominant-negative protein that abrogates wild-type BCL11B's ability to bind DNA, arresting T-cell development and disrupting hematopoietic stem cell migration; this reveals a prethymic role for BCL11B in hematopoietic progenitor migration. Exome sequencing, functional assays in human HSCs, zebrafish bcl11ba knockout rescue with wild-type vs. mutant human BCL11B The New England journal of medicine High 27959755
2010 Bcl11b controls antigen-dependent CD8+ T cell clonal expansion and cytolytic activity; it directly binds the E8I, E8IV, and E8V enhancers (but not E8II/E8III) to maintain optimal CD8 coreceptor expression, and Bcl11b-deficient CD8 T cells show deregulated Plcgamma1 and reduced granzyme B and perforin. ChIP (enhancer binding), conditional knockout, viral infection model, flow cytometry, cytotoxicity assay The Journal of experimental medicine High 20660613
2011 Bcl11b in DP thymocytes controls iNKT cell positive selection by regulating glycolipid self-antigen presentation via control of lysosomal gene expression; Bcl11b-deficient DP thymocytes show enlarged lysosomes, accumulation of glycosphingolipids, and altered expression of lysosomal proteins including cathepsins and Niemann-Pick genes. Conditional knockout, electron microscopy, flow cytometry, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 21444811
2013 BCL11B functions as a transcriptional repressor in Ewing sarcoma through the NuRD co-repressor complex; it contributes to the EWS/FLI repressed gene signature and represses SPRY1, whose re-expression limits Ewing sarcoma transformation capacity. ChIP, siRNA knockdown, re-expression experiments, colony formation assay PloS one Medium 23527175
2007 Bcl11b-knockdown T-cell lines show apoptosis in S phase with decreased p27 and Bcl-xL due to transcriptional repression, linked to impairment of Sirt1 (a NAD+-dependent deacetylase that associates with Bcl11b); this leads to Claspin cleavage and failure to phosphorylate Chk1, implicating Bcl11b in DNA replication stress response and genomic integrity maintenance. siRNA knockdown, Sirt1 co-immunoprecipitation, cell cycle analysis, Chk1 phosphorylation assay, UV irradiation of Bcl11b-/- thymocytes Oncogene Medium 17369851
2015 Bcl11b directly represses Id2 in early T-lineage cells to prevent innate lymphoid/NK fate adoption, but in ILC2s Bcl11b and Id2 are co-expressed; Bcl11b binding shows cell-type-specific genomic occupancy patterns and controls entirely different target gene sets in pro-T cells vs. ILC2s, and carries cell-type-specific post-translational modifications and protein complex compositions. ChIP-seq, conditional knockout in both lineages, mass spectrometry of protein complexes, reporter assays The Journal of experimental medicine High 31653691
2015 Bcl11b acts directly upstream of Gfi1 to maintain its expression in mature ILC2s; in the absence of Bcl11b, Gata3 and IL-33 receptor (Il1rl1) are downregulated, and Bcl11b independently represses the ILC3 transcription factor Ahr to maintain ILC2 lineage fidelity. Conditional Bcl11b knockout in ILC2s, gene expression profiling, ChIP (direct regulation of Gfi1 and Ahr), cytokine assays Immunity High 26231117
2017 Bcl11b primes the ThPOK and Runx3 lineage-specifying genes prior to TCR selection, with initial Thpok repression dependent on the last zinc finger motif of Bcl11b (distinct from the zinc finger required for T-lineage commitment), thereby coupling TCR MHC-restriction signals to the transcriptional program for CD4/CD8 lineage choice. Bcl11b conditional knockout, zinc finger point mutant (Bcl11b F/S826G), reporter assays, TCR-transgenic rescue Nature communications High 28951542
2018 Bcl11b binds GATA3 through protein-protein interaction and co-localizes with GATA3 at cis-regulatory elements in Th2 cells; Bcl11b-deficient Th2 cells show GATA3-dependent upregulation of IL-4, IL-5, and IL-13, indicating Bcl11b limits GATA3-mediated type 2 cytokine gene expression. Co-IP (protein-protein interaction), ChIP-seq, RNA-seq, conditional knockout The Journal of experimental medicine High 29514917
2018 Bcl11b maintains chromatin accessibility at Th2-cytokine promoters and locus-control regions, binds the Il4 HS IV silencer to reduce its accessibility, binds GATA3 intronic/downstream noncoding sites to sustain Gata3 expression, and binds/deactivates upstream Runx3 enhancers to restrict Runx3 expression and its repressive activity at Il4 HS IV. ATAC-seq, ChIP, conditional knockout, helminth infection model Nature communications High 29700302
2011 Genome-wide ChIP-seq in striatal cells identifies Bcl11b binding sites predominantly within 10 kb of transcription start sites; integration with expression profiling identifies 248 direct Bcl11b targets including components of the BDNF/neurotrophin signaling pathway, and reveals consensus DNA-binding motifs for Bcl11b. ChIP-seq, microarray expression profiling, Bcl11b overexpression PloS one Medium 21912641
2009 Ctip2/BCL11B is required for ameloblast formation in tooth development; it controls expression of amelogenin, ameloblastin, enamelin, Msx2, and epiprofin, and regulates ameloblast morphology, polarization, and adhesion properties. Conditional and germline Ctip2 knockout, immunohistochemistry, in situ hybridization, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 19251658
2012 Ctip2 controls keratinocyte proliferation and differentiation by directly and positively regulating EGFR transcription in proliferating cells and Notch1 transcription in differentiating cells; EGFR signaling downregulates Ctip2 mRNA, while high calcium signaling triggers Ctip2 SUMOylation, ubiquitination and proteasomal degradation, forming a negative feedback loop. ChIP (EGFR and Notch1 promoter occupancy), knockdown/overexpression, Western blot, promoter reporter assay Journal of cell science High 23015591
2012 Ctip2 is recruited to promoters of sphingolipid biosynthesis genes in developing skin and regulates epidermal ceramide and sphingomyelin composition; loss of Ctip2 alters major epidermal lipid species as measured by targeted lipidomics. ChIP, targeted lipidomics by mass spectrometry, Ctip2 knockout mouse The Journal of investigative dermatology Medium 23096701
2012 Keratinocytic Ctip2 directly represses TSLP transcription as demonstrated by ChIP; Ctip2 deletion leads to TSLP upregulation, triggering atopic dermatitis-like skin inflammation with Th2-type cytokine responses and immune cell infiltration. Conditional epidermal Ctip2 knockout, ChIP (TSLP promoter), histology, cytokine profiling PloS one Medium 23284675
2015 Bcl11b acts as a SWI/SNF complex subunit and regulates intestinal adenoma development; Bcl11b attenuation in Lgr5+ crypt base columnar cells increases expression of β-catenin target genes (c-Myc, cyclin D1), and BCL11B introduction in human cell lines downregulates β-catenin target gene transcription. Bcl11b heterozygous mice crossed to ApcMin/+, reporter assays, gene expression analysis in intestinal stem cells Carcinogenesis Medium 25827435
2019 HIV-1 Vpr promotes proteasomal degradation of CTIP2 in microglial cells and CD4+ T cells via association with the Cul4A-DDB1-DCAF1 ubiquitin ligase complex, targeting CTIP2 at the latent HIV-1 promoter where it is associated with heterochromatin-promoting enzymes, thereby reactivating HIV-1 expression. Co-IP, proteasome inhibitor treatment, ChIP, siRNA/dominant-negative experiments in microglial HIV-1 latency model Scientific reports Medium 31511615
2019 Bcl11b determines odorant receptor class choice in olfactory sensory neurons: loss-of-function biases OR choice toward class I (default), while gain-of-function biases toward class II; Bcl11b promotes class II OR expression by suppressing the activity of the J-element, a class I-OR enhancer. OSN-specific conditional Bcl11b knockout and overexpression, single-cell analysis, enhancer reporter assays, innate olfactory behavior assays Communications biology High 31396576
2019 CTIP2-deficient human medium spiny neurons derived from hPSCs show substantial reduction in phosphorylation of DARPP32 and GluR1 (two PKA targets), implicating CTIP2 in regulating PKA signaling in striatal neurons; transcriptomic analysis confirms CTIP2 targets are at the core of cAMP-Ca2+ signal integration in the PKA pathway. CTIP2-deficient human PSC-derived MSNs, phosphoprotein analysis, transcriptomics, HD mouse model comparison Stem cell reports Medium 31447328
2024 BCL11B succeeds PU.1 in a transcription factor 'relay' to maintain mSWI/SNF chromatin remodeling complex occupancy together with RUNX1 at T effector loci after PU.1 silencing during T lineage commitment, thereby poising the T cell effector chromatin landscape early in development. ChIP-seq, ATAC-seq, conditional knockout of PU.1 and BCL11B, mSWI/SNF co-immunoprecipitation Nature immunology High 38632339

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b. Science (New York, N.Y.) 311 20595614
2003 Bcl11b is required for differentiation and survival of alphabeta T lymphocytes. Nature immunology 300 12717433
2007 Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. The EMBO journal 296 17245431
2010 Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science (New York, N.Y.) 290 20538915
2008 The Fezf2-Ctip2 genetic pathway regulates the fate choice of subcortical projection neurons in the developing cerebral cortex. Proceedings of the National Academy of Sciences of the United States of America 279 18678899
2008 Ctip2 controls the differentiation of medium spiny neurons and the establishment of the cellular architecture of the striatum. The Journal of neuroscience : the official journal of the Society for Neuroscience 262 18199763
2011 The BCL11B tumor suppressor is mutated across the major molecular subtypes of T-cell acute lymphoblastic leukemia. Blood 161 21878675
2021 Enhancer Hijacking Drives Oncogenic BCL11B Expression in Lineage-Ambiguous Stem Cell Leukemia. Cancer discovery 156 34103329
2015 Transcription Factor Bcl11b Controls Identity and Function of Mature Type 2 Innate Lymphoid Cells. Immunity 143 26231117
2015 Bcl11b is essential for group 2 innate lymphoid cell development. The Journal of experimental medicine 137 25964370
2015 The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development. The Journal of experimental medicine 134 25964371
2004 CTIP1 and CTIP2 are differentially expressed during mouse embryogenesis. Gene expression patterns : GEP 132 15465497
2007 BCL11B is required for positive selection and survival of double-positive thymocytes. The Journal of experimental medicine 117 17998389
2016 Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment. Nature immunology 111 27376470
2013 A far downstream enhancer for murine Bcl11b controls its T-cell specific expression. Blood 105 23741008
2003 Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas. Biochemical and biophysical research communications 104 12565905
2016 Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B. The New England journal of medicine 102 27959755
2009 p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1. Oncogene 101 19581932
2012 A dual function of Bcl11b/Ctip2 in hippocampal neurogenesis. The EMBO journal 99 22588081
2010 Critical roles of Bcl11b in T-cell development and maintenance of T-cell identity. Immunological reviews 93 20969590
2018 BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells. Brain : a journal of neurology 92 29985992
2016 A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland. Cell stem cell 92 28041896
2006 CTIP2 associates with the NuRD complex on the promoter of p57KIP2, a newly identified CTIP2 target gene. The Journal of biological chemistry 86 16950772
2014 The multifaceted roles of Bcl11b in thymic and peripheral T cells: impact on immune diseases. Journal of immunology (Baltimore, Md. : 1950) 75 25128552
2013 CTIP2 is a negative regulator of P-TEFb. Proceedings of the National Academy of Sciences of the United States of America 75 23852730
2011 Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease. The Journal of experimental medicine 72 21875956
2011 Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium. Circulation. Cardiovascular genetics 72 22068335
2021 14q32 rearrangements deregulating BCL11B mark a distinct subgroup of T-lymphoid and myeloid immature acute leukemia. Blood 71 33876209
2021 The transcription factor Bcl11b promotes both canonical and adaptive NK cell differentiation. Science immunology 70 33712472
2012 The CB(1) cannabinoid receptor drives corticospinal motor neuron differentiation through the Ctip2/Satb2 transcriptional regulation axis. The Journal of neuroscience : the official journal of the Society for Neuroscience 68 23175820
2006 Inhibition of BCL11B expression leads to apoptosis of malignant but not normal mature T cells. Oncogene 68 17173069
2011 LSD1 cooperates with CTIP2 to promote HIV-1 transcriptional silencing. Nucleic acids research 66 22067449
2003 Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells. Journal of virology 65 12692243
2014 Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation. Nature communications 59 24739528
2017 Bcl11b-A Critical Neurodevelopmental Transcription Factor-Roles in Health and Disease. Frontiers in cellular neuroscience 58 28424591
2020 Cell type-specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells. The Journal of experimental medicine 56 31653691
2012 Role of the transcription factor Bcl11b in development and lymphomagenesis. Proceedings of the Japan Academy. Series B, Physical and biological sciences 55 22450536
2011 Bcl11b/Ctip2 controls the differentiation of vomeronasal sensory neurons in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 21752992
2009 Ctip2/Bcl11b controls ameloblast formation during mammalian odontogenesis. Proceedings of the National Academy of Sciences of the United States of America 54 19251658
2017 The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation. Leukemia 52 28232744
2010 Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b. The Journal of experimental medicine 51 20660613
2012 Delayed cutaneous wound healing and aberrant expression of hair follicle stem cell markers in mice selectively lacking Ctip2 in epidermis. PloS one 50 22383956
2011 Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling. PloS one 49 21912641
2017 Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes. Nature communications 48 28951542
2014 HMGA1 recruits CTIP2-repressed P-TEFb to the HIV-1 and cellular target promoters. Nucleic acids research 47 24623795
2007 Haploinsufficiency of Bcl11b for suppression of lymphomagenesis and thymocyte development. Biochemical and biophysical research communications 47 17306224
2018 Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation. The Journal of experimental medicine 46 29514917
2003 Activation of HOX11L2 by juxtaposition with 3'-BCL11B in an acute lymphoblastic leukemia cell line (HPB-ALL) with t(5;14)(q35;q32.2). Genes, chromosomes & cancer 46 12661009
2010 The corticofugal neuron-associated genes ROBO1, SRGAP1, and CTIP2 exhibit an anterior to posterior gradient of expression in early fetal human neocortex development. Cerebral cortex (New York, N.Y. : 1991) 44 21060114
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2012 The role of BCL11B in hematological malignancy. Experimental hematology & oncology 41 23211040
2011 Transcription factor Bcl11b controls selection of invariant natural killer T-cells by regulating glycolipid presentation in double-positive thymocytes. Proceedings of the National Academy of Sciences of the United States of America 41 21444811
2006 HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32). Blood 41 16926283
2007 Lack of Bcl11b tumor suppressor results in vulnerability to DNA replication stress and damages. Oncogene 40 17369851
2013 BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma. PloS one 38 23527175
2012 Selective ablation of Ctip2/Bcl11b in epidermal keratinocytes triggers atopic dermatitis-like skin inflammatory responses in adult mice. PloS one 35 23284675
2004 Involvement of V(D)J recombinase in the generation of intragenic deletions in the Rit1/Bcl11b tumor suppressor gene in gamma-ray-induced thymic lymphomas and in normal thymus of the mouse. Carcinogenesis 35 14754877
2018 Bcl11b is essential for licensing Th2 differentiation during helminth infection and allergic asthma. Nature communications 33 29700302
2016 Structure-function integrity of the adult hippocampus depends on the transcription factor Bcl11b/Ctip2. Genes, brain, and behavior 32 26915960
2012 Ctip2 is a dynamic regulator of epidermal proliferation and differentiation by integrating EGFR and Notch signaling. Journal of cell science 32 23015591
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2019 A De Novo heterozygous frameshift mutation identified in BCL11B causes neurodevelopmental disorder by whole exome sequencing. Molecular genetics & genomic medicine 31 31347296
2007 Expression of COUP-TF-interacting protein 2 (CTIP2) in mouse skin during development and in adulthood. Gene expression patterns : GEP 31 17631058
2019 Bcl11b controls odorant receptor class choice in mice. Communications biology 29 31396576
2019 Bcl11b prevents fatal autoimmunity by promoting Treg cell program and constraining innate lineages in Treg cells. Science advances 29 31457080
2011 Down regulation of BCL11B expression inhibits proliferation and induces apoptosis in malignant T cells by BCL11B-935-siRNA. Hematology (Amsterdam, Netherlands) 29 21756541
2018 The N-Terminal CCHC Zinc Finger Motif Mediates Homodimerization of Transcription Factor BCL11B. Molecular and cellular biology 28 29203643
2019 HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing. Scientific reports 27 31511615
2009 CTIP2 expression in human head and neck squamous cell carcinoma is linked to poorly differentiated tumor status. PloS one 27 19399189
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2015 BCL11B/CTIP2 is highly expressed in GABAergic interneurons of the mouse somatosensory cortex. Journal of chemical neuroanatomy 26 26698402
2012 BCL11B regulates epithelial proliferation and asymmetric development of the mouse mandibular incisor. PloS one 26 22629441
2022 Transcription factors Bcl11a and Bcl11b are required for the production and differentiation of cortical projection neurons. Cerebral cortex (New York, N.Y. : 1991) 25 34963132
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2017 Gga-miR-219b targeting BCL11B suppresses proliferation, migration and invasion of Marek's disease tumor cell MSB1. Scientific reports 25 28652615
2016 HIC1 controls cellular- and HIV-1- gene transcription via interactions with CTIP2 and HMGA1. Scientific reports 25 27725726
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2012 Transcription factor Ctip2 controls epidermal lipid metabolism and regulates expression of genes involved in sphingolipid biosynthesis during skin development. The Journal of investigative dermatology 24 23096701
2020 miR-21-5p promotes cell proliferation by targeting BCL11B in Thp-1 cells. Oncology letters 23 33376550
2019 CTIP2-Regulated Reduction in PKA-Dependent DARPP32 Phosphorylation in Human Medium Spiny Neurons: Implications for Huntington Disease. Stem cell reports 23 31447328
2018 Downregulated miR-17, miR-29c, miR-92a and miR-214 may be related to BCL11B overexpression in T cell acute lymphoblastic leukemia. Asia-Pacific journal of clinical oncology 23 29749698
2015 Bcl11b SWI/SNF-complex subunit modulates intestinal adenoma and regeneration after γ-irradiation through Wnt/β-catenin pathway. Carcinogenesis 21 25827435
2018 Genomics of neonatal sepsis: has-miR-150 targeting BCL11B functions in disease progression. Italian journal of pediatrics 20 30497506
2013 Reduced level of the BCL11B protein is associated with adult T-cell leukemia/lymphoma. PloS one 20 23383087
2021 Human Adipose-derived mesenchymal stem cells promote lymphocyte apoptosis and alleviate atherosclerosis via miR-125b-1-3p/BCL11B signal axis. Annals of palliative medicine 19 33725769
2020 Bcl11b/Ctip2 in Skin, Tooth, and Craniofacial System. Frontiers in cell and developmental biology 19 33363142
2019 Chimeric antigen receptor-induced BCL11B suppression propagates NK-like cell development. The Journal of clinical investigation 19 31479431
2016 Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection. Frontiers in immunology 19 27790219
2024 PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape. Nature immunology 18 38632339
2021 Redefining the biological basis of lineage-ambiguous leukemia through genomics: BCL11B deregulation in acute leukemias of ambiguous lineage. Best practice & research. Clinical haematology 18 34865701
2020 High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma. Cancers 18 32164354
2018 Bcl11b Regulates IL-17 Through the TGF-β/Smad Pathway in HDM-Induced Asthma. Allergy, asthma & immunology research 18 30088373
2016 N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain. Scientific reports 18 27577752
2020 BCL11B suppresses tumor progression and stem cell traits in hepatocellular carcinoma by restoring p53 signaling activity. Cell death & disease 17 33093445
2016 Identification of BCL11B as a regulator of adipogenesis. Scientific reports 17 27586877
2014 Bcl11b prevents the intrathymic development of innate CD8 T cells in a cell intrinsic manner. International immunology 17 25422283
2012 The role of BCL11B in regulating the proliferation of human naive T cells. Human immunology 17 22426257
2010 Proteome analysis reveals new mechanisms of Bcl11b-loss driven apoptosis. Journal of proteome research 17 20513151
2009 Haploinsufficiency and acquired loss of Bcl11b and H2AX induces blast crisis of chronic myelogenous leukemia in a transgenic mouse model. Cancer science 17 19432895