Zbtb32

Bovine leukemia virus (BLV) is a member of the genus Deltaretrovirus within the family Retroviridae that infects bovine B cells, causing persistent lymphocytosis and enzootic bovine leukosis (EBL) in a small fraction of infected cattle. As changes in the transcriptome of infected cells are important for BLV disease progression, comprehensive analysis of gene expression in different disease states is required. In this study, we performed an RNA-seq analysis using samples from non-EBL cattle with and without BLV infection...

The family of genes containing C2H2 zinc finger domains, which has more than 700 members, is one of the largest in the genome. Of particular interest are C2H2 genes with potential tissue-specific transcription, which determine the functional properties of individual cell types, including those associated with pathological processes. The aim of this work was to identify C2H2 family genes with tissue-specific transcription and analyze changes in their activity during tumor progression. To search for these genes, we used four databases containing data on gene transcription in human tissues obtained by RNA-Seq analysis...

Fanconi anemia (FA) pathway is a typical and multienzyme-regulated DNA damage repairer that influences the occurrence and development of disease including cancers. Few comprehensive analyses were reported about the role of FA-related genes (FARGs) and their prognostic values in cancers. In this study, a comprehensive pan-cancer analysis on 79 FARGs was performed. According to the correlation analyses between HPV integration sites and FARGs, we found that FARGs played specific and critical roles in HPV-related cancers, especially in cervical cancer (CC)...

The hypothalamic-pituitary-adrenal (HPA) axis forms a complex neuroendocrine system that regulates the body's response to stress such as starvation. In contrast with the glucocorticoid receptor (GR), Zinc finger and BTB domain containing 32 (ZBTB32) is a transcription factor with poorly described functional relevance in physiology. This study shows that ZBTB32 is essential for the production of glucocorticoids (GCs) in response to starvation, since ZBTB32-/- mice fail to increase their GC production in the absence of nutrients...

Members of the broad complex, tram track, bric-a-brac and zinc finger (BTB-ZF) family of transcription factors, such as BCL-6, ZBTB20, and ZBTB32, regulate antigen-specific B cell differentiation, plasma cell longevity, and the duration of antibody production. We found that ZBTB38, a different member of the BTB-ZF family that binds methylated DNA at CpG motifs, is highly expressed by germinal center B cells and plasma cells. To define the functional role of ZBTB38 in B cell responses, we generated mice conditionally deficient in this transcription factor...

Splenic marginal zone lymphoma (SMZL) is a rare, indolent non-Hodgkin's lymphoma that affects 0. 13 per 100,000 persons annually. Overall survival of SMZL is estimated to reach 8-11 years in most cases, but up to 30% of SMZL cases develop aggressive presentations resulting in greatly diminished time of survival. SMZL presents with a very heterogeneous molecular profile, making diagnosis problematic, and accurate prognosis even less likely. The study herein has identified a potential diagnostic gene expression signature with highly specific predictive utility, coined the SMZL-specific Gene Expression Signature (SSGES)...

ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed responses by Zbtb32-/- mice or bone marrow chimeras against a panel of chronic and acute challenges. Mixed bone marrow chimeras were established in which all B cells were derived from either Zbtb32-/- mice or control littermates. Chronic infection of Zbtb32-/- chimeras with murine cytomegalovirus led to nearly 20-fold higher antigen-specific IgG2b levels relative to controls by week 9 post-infection, despite similar viral loads...

Natural killer (NK) cells are innate lymphocytes that display features of adaptive immunity during viral infection. Biallelic mutations in IRF8 have been reported to cause familial NK cell deficiency and susceptibility to severe viral infection in humans; however, the precise role of this transcription factor in regulating NK cell function remains unknown. Here, we show that cell-intrinsic IRF8 was required for NK-cell-mediated protection against mouse cytomegalovirus infection. During viral exposure, NK cells upregulated IRF8 through interleukin-12 (IL-12) signaling and the transcription factor STAT4, which promoted epigenetic remodeling of the Irf8 locus...

Background : We previously identified the transcriptional regulator Zbtb32 as a factor that can promote T cell tolerance in the Non-Obese Diabetic (NOD) mouse, a model of Type 1 diabetes. Antigen targeted to DCIR2 + dendritic cells (DCs) in vivo inhibited both diabetes and effector T cell expansion in NOD mice. Furthermore, Zbtb32 was preferentially induced in autoreactive CD4 T cells stimulated by these tolerogenic DCIR2 + DCs, and overexpression of Zbtb32 in islet-specific T cells inhibited the diabetes development by limiting T cell proliferation and cytokine production...

The large ZBTB family comprises a diverse group of transcriptional factors. Several ZBTB proteins have emerged as critical factors that regulate the lineage commitment, differentiation, and function of lymphoid cells as well as many other developmental events. For instance, dysfunctions of ZBTB20 or ZBTB24 have been linked to multisystem failures in humans. Within the B-cell lineage, BCL6, ZBTB7A, ZBTB17, and ZBTB1 regulate the development/differentiation of B cells in both bone marrow and peripheral lymphoid organs, while ZBTB20 and ZBTB32 seem to mainly impact the maintenance of terminal plasma cells...

Virus infections induce CD8+ T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8+ T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8+ T cells. After acute virus infection, CD8+ T cells deficient in ZBTB32 showed enhanced virus-specific CD8+ T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation...

The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to GATA3 promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for down-regulation of GATA3 via ZPO2...

Memory B cell responses are more rapid and of greater magnitude than are primary Ab responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of Ab recall responses. ZBTB32 is highly expressed by mouse and human memory B cells but not by their naive counterparts. Zbtb32(-/-) mice mount normal primary Ab responses to T-dependent Ags. However, Zbtb32(-/-) memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses...

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4(+) memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter...

Immunological memory is a hallmark of the adaptive immune system. Although natural killer (NK) cells have traditionally been classified as a component of the innate immune system, they have recently been shown in mice and humans to exhibit certain features of immunological memory, including an ability to undergo a clonal-like expansion during virus infection, generate long-lived progeny (i.e. memory cells), and mediate recall responses against previously encountered pathogens--all characteristics previously ascribed only to adaptive immune responses by B and T cells in mammals...

During autoimmunity, the normal ability of dendritic cells (DCs) to induce T-cell tolerance is disrupted; therefore, autoimmune disease therapies based on cell types and molecular pathways that elicit tolerance in the steady state may not be effective. To determine which DC subsets induce tolerance in the context of chronic autoimmunity, we used chimeric antibodies specific for DC inhibitory receptor 2 (DCIR2) or DEC-205 to target self-antigen to CD11b(+) (cDC2) DCs and CD8(+) (cDC1) DCs, respectively, in autoimmune-prone nonobese diabetic (NOD) mice...

Abnormal DNA methylation is known as playing an important role in the tumorgenesis. It is helpful for distinguishing the specificity of diagnosis and therapeutic targets for cancers based on characteristics of DNA methylation patterns across cancers. High throughput DNA methylation analysis provides the possibility to comprehensively filter the epigenetics diversity across various cancers. We integrated whole-genome methylation data detected in 798 samples from seven cancers. The hierarchical clustering revealed the existence of cancer-specific methylation pattern...

Natural killer (NK) cells are innate lymphocytes that exhibit many features of adaptive immunity, including clonal proliferation and long-lived memory. Here we demonstrate that the BTB-ZF transcription factor Zbtb32 (also known as ROG, FAZF, TZFP and PLZP) was essential for the proliferative burst and protective capacity of virus-specific NK cells. Signals from proinflammatory cytokines were both necessary and sufficient to induce high expression of Zbtb32 in NK cells. Zbtb32 facilitated NK cell proliferation during infection by antagonizing the anti-proliferative factor Blimp-1 (Prdm1)...

The aims of this study were: (1) to identify candidate single-nucleotide polymorphisms (SNPs) and mechanisms of major depressive disorder (MDD) and (2) to generate SNP-to-gene-to-pathway hypotheses. An MDD genome-wide association study (GWAS) data set that included 365,419 SNPs in 1,821 MDD cases and 1,822 controls of European descent was used in this study. Identify Candidate Causal SNPs and Pathway (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 21 candidate SNPs, 16 genes, and 5 pathways, which provided 16 hypothetical biological mechanisms...

Cell of origin classification of diffuse large B-cell lymphoma (DLBCL) identifies subsets with biological and clinical significance. Despite the established nature of the classification existing studies display variability in classifier implementation, and a comparative analysis across multiple data sets is lacking. Here we describe the validation of a cell of origin classifier for DLBCL, based on balanced voting between 4 machine-learning tools: the DLBCL automatic classifier (DAC). This shows superior survival separation for assigned Activated B-cell (ABC) and Germinal Center B-cell (GCB) DLBCL classes relative to a range of other classifiers...