Bach2 is required for B cell and T cell memory differentiation

Sidwell, Tom; Kallies, Axel

doi:10.1038/ni.3493

Cited by 17 publications

(15 citation statements)

References 12 publications

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“…BACH2 was established as a crucial factor for B-and T-cell memory differentiation. Nevertheless, the potential roles of these transcription factors during embryogenesis remain obscure (Sidwell & Kallies, 2016). Members of the BACH family possess both a BTB/POZ and a CNC-bZip functional domain, conferring them with protein-protein interaction and DNA-binding capabilities (Zhou et al, 2016) to the antioxidant response elements (Zhou et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In mammals, BACH1 is expressed ubiquitously and has been shown to act either as an activator or repressor of transcription and to be involved in oxidative stress, metabolism, cell transformation, neurodegenerative diseases, tumor expansion, and metastatic spread (Watari et al, 2008;Warnatz et al, 2011;Nakanome et al, 2013;Igarashi & Watanabe-Matsui, 2014;Lee et al, 2014;Zhou et al, 2016;Lee et al, 2019;Lignitto et al, 2019;Wiel et al, 2019). BACH2 is a transcriptional repressor crucial for the terminal differentiation and maturation of both T and B lymphocytes (Sidwell & Kallies, 2016), and its loss is associated with severe autoimmune diseases. BACH proteins are highly conserved in vertebrates, particularly in the functional (BTB and bZip) domains and the regions immediately surrounding them (Igarashi & Watanabe-Matsui, 2014).…”

Section: Spatial and Temporal Expression Of Bach2 During Zebrafish Dementioning

confidence: 99%

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BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

Cohen¹,

Tempelhof²,

Raz

et al. 2020

Life Sci. Alliance

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Angiogenesis and lymphangiogenesis are key processes during embryogenesis as well as under physiological and pathological conditions. Vascular endothelial growth factor C (VEGFC), the ligand for both VEGFR2 and VEGFR3, is a central lymphangiogenic regulator that also drives angiogenesis. Here, we report that members of the highly conserved BACH (BTB and CNC homology) family of transcription factors regulate VEGFC expression, through direct binding to its promoter. Accordingly, down-regulation of bach2a hinders blood vessel formation and impairs lymphatic sprouting in a Vegfc-dependent manner during zebrafish embryonic development. In contrast, BACH1 overexpression enhances intratumoral blood vessel density and peritumoral lymphatic vessel diameter in ovarian and lung mouse tumor models. The effects on the vascular compartment correlate spatially and temporally with BACH1 transcriptional regulation of VEGFC expression. Altogether, our results uncover a novel role for the BACH/VEGFC signaling axis in lymphatic formation during embryogenesis and cancer, providing a novel potential target for therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Spatial and Temporal Expression Of Bach2 During Zebrafish Dementioning

confidence: 99%

BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

Cohen¹,

Tempelhof²,

Raz

et al. 2020

Life Sci. Alliance

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“…Moreover, BATF and IRF1 are induced early during in vitro regulatory T (Treg) cell differentiation and act as pioneer factors for the differentiation of type 1 Treg (Tr1) cells ( 64 ). BACH2, like AP-1 factors that contain a bZIP domain, can regulate CD8 + T cell differentiation by controlling the access of AP-1 factors to enhancers, thus limiting the expression of TCR-driven genes by attenuating the availability of AP-1 sites to JUN family TFs ( 65 , 66 ).…”

Section: Interplay Of Chromatin and Transcription Factors Ap-1 Irf4mentioning

confidence: 99%

Chromatin Accessibility and Interactions in the Transcriptional Regulation of T Cells

Li,

Leonard

2018

Front. Immunol.

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During T cell differentiation and activation, specific stimuli, and a network of transcription factors (TFs) are involved in orchestrating chromatin accessibility, establishing enhancer-promoter interactions, and regulating gene expression. Over the past few years, there have been new insights into how chromatin interactions coordinate differentiation during T cell development and how regulatory elements are programmed to allow T cells to differentially respond to distinct stimuli. In this review, we discuss recent advances related to the roles of TFs in establishing the regulatory chromatin landscapes that orchestrate T cell development and differentiation. In particular, we focus on the role of TFs (e.g., TCF-1, BCL11B, PU.1, STAT3, STAT5, AP-1, and IRF4) in mediating chromatin accessibility and interactions and in regulating gene expression in T cells, including gene expression that is dependent on IL-2 and IL-21. Furthermore, we discuss the state of knowledge on enhancer-promoter interactions and how autoimmune disease risk variants can be linked to molecular functions of putative target genes.

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“…This was demonstrated by the experiments done in mice which showed, BACH2 gene expression is highly sensitive to transcription-blocking in DNA lesions caused by UV irradiation in dermal fibroblasts from aged mice [16]. BACH2 has been shown to be involved in B-cell and memory CD4+ T-cell differentiation and inhibit effector cell functions by limiting antigen-receptor-stimulation-induced gene expression and restricting premature expression of the transcriptional regulator PRDM1 (PR domain zinc finger protein 1) [17]. PRDM1 is necessary for terminal differentiation of antibody-secreting plasma cells, while in T-cells, it has been shown to regulate homeostasis of effector and memory CD4+ T-cells [18].…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in the BACH2 and PRDM1 genes in lymphocytes from healthy donors and chronic lymphocytic leukemia patients

et al. 2019

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BackgroundAge-related genetic changes in lymphocyte subsets are not currently well documented. BACH2 is a transcription factor that plays an important role in immune-mediated homeostasis by tightly regulating PRDM1 expression in both B-cells and T-cells. BACH2 gene expression is highly sensitive to DNA damage in aged mice. This concept led us to investigate the variation in BACH2 and also PRDM1 expression in major lymphocyte subsets with age.MethodsLymphocyte subsets from 60 healthy donors, aged from 20 to 90 years, and 41 untreated chronic lymphocytic leukemia patients were studied. BACH2 and PRDM1 gene expression was analyzed by real-time quantitative PCR. BACH2 gene expression was correlated with its protein expression. Lymphocyte apoptosis was evaluated after intracellular oxidative stress-inducing etoposide treatment of T and B cells.ResultsOur analysis shows BACH2 mRNA downregulation with age in healthy donor CD4+, CD8+ T-cells and CD19+ B-cells. Decreased BACH2 expression was also correlated with an age-related reduction in CD8 + CD28+ T-cells. We found a strong correlation between age-related BACH2 downregulation and decreased CD4+ T-cell and CD19+ B-cell apoptosis. PRDM1, as expected, was significantly upregulated in CD4+ T-cells, CD8+ T-cells and CD19+ B-cells, and inversely correlated with BACH2. A comparison of untreated chronic lymphocytic leukemia patients with age-matched healthy donors reveals that BACH2 mRNA expression was further reduced in CD4+ T-cells, CD8+ T-cells and leukemic-B cells. PRDM1 gene expression was consequently significantly upregulated in CD4+ and CD8+ T-cells in chronic lymphocytic leukemia patients but not in their leukemic B-cells.ConclusionOverall, our data suggest that BACH2 and PRDM1 genes are significantly correlated with age in human immune cells and may be involved in immunosenescence.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5276-2) contains supplementary material, which is available to authorized users.

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Bach2 is required for B cell and T cell memory differentiation

Cited by 17 publications

References 12 publications

BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

Chromatin Accessibility and Interactions in the Transcriptional Regulation of T Cells

Age-related changes in the BACH2 and PRDM1 genes in lymphocytes from healthy donors and chronic lymphocytic leukemia patients

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