| 2012 |
Zbtb46 is selectively expressed by classical DCs (cDCs) and committed cDC progenitors (pre-cDCs) but not by plasmacytoid DCs, monocytes, macrophages, or other immune lineages. Overexpression of Zbtb46 in bone marrow progenitors inhibited granulocyte potential and promoted cDC development. Zbtb46-deficient cDCs maintained expression of G-CSF and LIF receptors that are normally downregulated in cDCs, indicating Zbtb46 enforces cDC identity by restricting responsiveness to non-DC growth factors. |
Homologous recombination (GFP knockin), bone marrow progenitor overexpression, Zbtb46-deficient mouse analysis, flow cytometry, developmental potential assays |
The Journal of experimental medicine |
High |
22615127
|
| 2012 |
zDC (Zbtb46/Btbd4) is specifically expressed by cDCs and committed cDC precursors but not monocytes, pDCs, or other immune cells. A DTR knockin at the zDC locus allows selective depletion of cDCs upon diphtheria toxin injection, sparing pDCs, monocytes, macrophages, and NK cells. |
DTR cDNA knockin into zDC locus, diphtheria toxin depletion, flow cytometry, bone marrow chimeras, immune challenge models (T. gondii, melanoma) |
The Journal of experimental medicine |
High |
22615130
|
| 2017 |
ZBTB46 is negatively regulated by androgen receptor (AR) signaling via miR-1-mediated downregulation in prostate cancer cells. ZBTB46 transcriptionally regulates SNAI1, a key EMT driver, thereby promoting epithelial-to-mesenchymal transition and metastasis after androgen deprivation. |
miRNA overexpression/knockdown, ZBTB46 overexpression/knockdown, transcriptional reporter assays, cell migration/invasion assays, in vivo tumor models |
Oncogene |
Medium |
28692046
|
| 2018 |
ZBTB46 acts as a transcriptional coactivator that binds to the promoter of PTGS1 (prostaglandin-endoperoxide synthase 1) and transcriptionally upregulates PTGS1 levels. ZBTB46 is regulated upstream by the androgen-responsive gene SPDEF, placing it in the AR-SPDEF-ZBTB46-PTGS1 axis during neuroendocrine prostate cancer differentiation. |
ChIP assay (ZBTB46 binding to PTGS1 promoter), ZBTB46 overexpression/knockdown, luciferase reporter, in vitro and in vivo tumor models, PTGS1 inhibitor sensitivity assays |
Cancer letters |
Medium |
30312731
|
| 2019 |
ZBTB46 transcriptionally activates LIF expression in prostate cancer cells by physically interacting with the regulatory sequence of the LIF gene. High ZBTB46 output activates LIF-STAT3 signaling, promoting neuroendocrine differentiation. ZBTB46 is induced by androgen deprivation therapy and is upregulated in high-grade prostate tumors. |
ChIP assay (ZBTB46 binding to LIF regulatory sequence), ZBTB46 overexpression/knockdown, LIF-STAT3 signaling assays, IHC on patient samples, serum LIF measurement |
Clinical cancer research |
Medium |
30962287
|
| 2022 |
ZBTB46 restrains the inflammatory properties of ILC3s in the intestine, including OX40L-dependent expansion of Th17 cells. ZBTB46 expression in CCR6+ ILC3s is imprinted by RORγt, fine-tuned by microbiota-derived signals, and increased by pro-inflammatory cytokines. ZBTB46+ ILC3s are a major source of IL-22, and their selective depletion renders mice susceptible to enteric infection. |
Single-cell transcriptomics, conditional cell depletion (DTR-based), genetic loss-of-function, T cell co-culture assays, intestinal infection models (enteric infection), IL-22 measurement |
Nature |
High |
35831503
|
| 2022 |
In zebrafish, Zbtb46 binds to a 5'-TGACGT-3' motif in the promoters of cd80/86 and cd40 genes in resting dendritic cells, where it establishes a repressive histone modification pattern (H3K4me0/H3K9me3/H3K27me3) by organizing NuRD (Mdb3/NuRD) and Hdac3/NCoR corepressor complexes through recruitment of Hdac1/2 and Hdac3. Upon TLR9 signaling, E3 ubiquitin ligase Cullin1/Fbxw11 mediates Zbtb46 degradation, releasing promoters for epigenetic reprogramming to an activated state (H3K4me3/H3K9ac/H3K27ac) and enabling CD80/86 and CD40 expression. |
ChIP-qPCR, mass spectrometry, Zbtb46 knockout zebrafish (CRISPR), co-immunoprecipitation, flow cytometry, T cell activation assays, TLR9 pathway analysis |
Journal of immunology |
High |
35675955
|
| 2022 |
During DC development from bone marrow precursors, cDC-primed cells within Ly6DhiZbtb46- precursors rapidly upregulate Zbtb46 and pass through a Zbtb46+Ly6D+ intermediate stage before acquiring cDC phenotype after cell division. Type I IFN arrests cDC-primed cells at the Zbtb46+Ly6D+ stage, limiting cDC output and promoting pDC output. |
Single-cell transcriptomics, high-dimensional flow cytometry, cell fate analysis (in vitro and in vivo), cytokine stimulation experiments |
Nature communications |
High |
35705536
|
| 2024 |
ZBTB46 controls tumor angiogenesis and anti-tumor immunity. In endothelial cells, Zbtb46 deficiency leads to a highly angiogenic phenotype (dysfunctional vasculature). In bone marrow progenitors, Zbtb46 deficiency upregulates Cebpb, diverting DC differentiation toward immunosuppressive myeloid lineage output. Enforced Zbtb46 expression normalizes tumor vessels and, by suppressing Cebpb, skews progenitors toward immunostimulatory myeloid output. Zbtb46 mRNA treatment synergized with anti-PD1 immunotherapy. |
Endothelial cell-specific and bone marrow-specific Zbtb46 knockout/overexpression, in vivo tumor models, transcriptomic analysis, Cebpb epistasis analysis, vascular normalization assays, anti-PD1 combination therapy |
Nature immunology |
High |
39134750
|
| 2020 |
Radiation-induced apoptotic bodies activate STAT5/Zbtb46 signaling in bone marrow progenitors, increasing Zbtb46 expression and enhancing subsequent DC immune-activating potential. Depletion of apoptotic bodies using annexin beads reversed these effects, confirming the apoptotic body → STAT5 → Zbtb46 pathway. |
In vitro irradiation of bone marrow progenitors, DC differentiation, apoptotic body depletion (annexin beads), flow cytometry, ELISA, adaptive dose experiments in vivo |
International journal of radiation biology |
Medium |
32396024
|
| 2021 |
PCK1 (phosphoenolpyruvate carboxykinase 1) is regulated by the ZBTB46 transcription factor upon activation of LIF signaling. ChIP analysis confirmed ZBTB46 binding at PCK1 regulatory regions. Upregulation of PCK1 reciprocally increases ZBTB46 levels, forming a positive feedback loop that promotes neuroendocrine differentiation in CRPC. |
RNA-seq, ChIP analysis (ZBTB46 binding to PCK1), in vitro cell lines, in vivo animal models, PCK1 inhibitor treatment |
British journal of cancer |
Medium |
34815524
|
| 2021 |
Forced expression of Zbtb46 in ESC-derived progenitors suppresses myeloid development (reduced CD11b+ cells, lower Irf8 and myeloid gene expression), interferes with mesoderm formation, and inhibits cell proliferation, while promoting erythroid colony formation and increasing adult hemoglobin (Hbb-b1) expression and CD105+ endothelial-like cell formation. |
Chemically inducible Zbtb46 overexpression in mouse ESC lines, flow cytometry, gene expression profiling, colony assays |
Stem cells |
Medium |
34058047
|
| 2025 |
Depletion of myeloid-derived Zbtb46+ cells (adipose tissue DCs) in obese mice improves glucose homeostasis via the DPP4/GLP-1 pathway. Adipose tissue DCs are a key contributor to circulating DPP4 activity; their depletion reduces DPP4 activity, elevates GLP-1 levels, enhances insulin secretion, and decreases food intake. DC-specific Dpp4 knockout confirmed that ATDC-derived DPP4 regulates GLP-1-induced insulin secretion. |
Zbtb46-DTR chimeric mice (bone marrow transplant), diphtheria toxin depletion, DC-specific Dpp4 knockout (Cre-loxP), GLP-1/DPP4 activity assays, glucose tolerance testing, insulin assays |
Journal of advanced research |
High |
41139017
|