The BTB-ZF transcription factors

Siggs, Owen M.; Beutler, Bruce

doi:10.4161/cc.21277

Cited by 121 publications

(114 citation statements)

References 137 publications

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“…MAZR, a member of the BTB-Pox virus and ZF domain containing a family of ZF transcription factors (23,24), is part of the transcription factor network regulating CD4/CD8 cell fate choice of DP thymocytes by repressing Thpok expression in MHC class I-signaled DP thymocytes (13). We observed that MAZR interacts with Runx proteins and hypothesized that MAZR and Runx/CBFb complexes might synergize in the repression of ThPOK (13).…”

Section: Mazr Interacts With the Ad Of Runx1 Via Zf7mentioning

confidence: 90%

MAZR and Runx Factors Synergistically Repress ThPOK during CD8+ T Cell Lineage Development

Sakaguchi

Hainberger

Tizian

et al. 2015

The Journal of Immunology

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Th-inducing Pox virus and zinc finger/Krüppel-like factor (ThPOK) is a key commitment factor for CD4+ lineage T cells and is essential for the maintenance of CD4 lineage integrity; thus, the expression of ThPOK has to be tightly controlled. In this article, we demonstrate that Myc-associated zinc finger-related factor (MAZR) and Runt-related transcription factor 1 (Runx1) together repressed ThPOK in preselection double-positive thymocytes, whereas MAZR acted in synergy with Runx3 in the repression of ThPOK in CD8+ T cells. Furthermore, MAZR-Runx1 and MAZR-Runx3 double-mutant mice showed enhanced derepression of Cd4 in double-negative thymocytes and in CD8+ T cells in comparison with Runx1 or Runx3 single-deficient mice, respectively, indicating that MAZR modulates Cd4 silencing. Thus, our data demonstrate developmental stage-specific synergistic activities between MAZR and Runx/core-binding factor β (CBFβ) complexes. Finally, retroviral Cre-mediated conditional deletion of MAZR in peripheral CD8+ T cells led to the derepression of ThPOK, thus showing that MAZR is also part of the molecular machinery that maintains a repressed state of ThPOK in CD8+ T cells.

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Section: Mazr Interacts With the Ad Of Runx1 Via Zf7mentioning

confidence: 90%

MAZR and Runx Factors Synergistically Repress ThPOK during CD8+ T Cell Lineage Development

Sakaguchi

Hainberger

Tizian

et al. 2015

The Journal of Immunology

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“…PATZ1 has an N-terminal BTB domain for protein interaction, a central DNA binding AT hook domain, and a second, C-terminal, zinc finger (ZF) DNA binding domain (9)(10)(11). A recent ChIP-Seq study identified that the PATZ1 binding consensus can be either AT rich or GC rich (12).…”

mentioning

confidence: 99%

PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function

Keskin

Deniz

Eryilmaz

et al. 2015

Molecular and Cellular Biology

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e Insults to cellular health cause p53 protein accumulation, and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of p53. The novel role of PATZ1 as an inhibitor of the p53 protein marks its gene as a proto-oncogene. PATZ1-deficient cells have reduced proliferative capacity, which we assessed by transcriptome sequencing (RNA-Seq) and real-time cell growth rate analysis. PATZ1 modifies the expression of p53 target genes associated with cell proliferation gene ontology terms. Moreover, PATZ1 regulates several genes involved in cellular adhesion and morphogenesis. Significantly, treatment with the DNA damage-inducing drug doxorubicin results in the loss of the PATZ1 transcription factor as p53 accumulates. We find that PATZ1 binds to p53 and inhibits p53-dependent transcription activation. We examine the mechanism of this functional inhibitory interaction and demonstrate that PATZ1 excludes p53 from DNA binding. This study documents PATZ1 as a novel player in the p53 pathway. Wild-type (WT) p53 is a stress-responsive, sequence-specific transcription factor that inhibits the cell cycle, promotes senescence, and, if the insult to cellular health is not resolved, induces apoptotic death (1). p53 mutations that allow cells to escape this death are the most common genetic event in human cancer (2). Alternative mechanisms of escape rely on the overexpression of MDM2 and MDMX, major negative regulators of p53 that keep p53 levels low under unstressed conditions through ubiquitination-mediated degradation (3). Moreover, many DNA tumor viruses encode proteins that can inactivate p53 (2). However, the list of p53 regulators is far from complete. Various stress conditions result in the upregulation of p53, controlled by feedback loops, posttranslational modifications, and epigenetic changes. In the present study, we aimed to find new players that modify p53 function.p53 is composed of an N-terminal transactivation domain (through which it interacts with MDM2), a proline-rich domain, central DNA binding and tetramerization domains, and a C-terminal regulatory domain. p53 binds response elements (REs) in nuclear DNA, which results in stress-induced changes (either upor downregulation) in gene expression. Tetrameric p53 binds REs that are composed of two half-sites, each with a consensus of RR RCWWGYYY, separated by 0 to 21 bases (where R is a purine, Y is a pyrimidine, and W is either an A or T) (4). p53 REs can be subcategorized as those that respond to low levels of wild-type p53, those that respond to stabilized p53 after stress, and those that respond to p53 with mutations in its DNA binding domain. A recent study found 160 p53 REs controlling 129 genes in the human genome (5). Another study using chromatin immunoprecipitation (ChIP) with paired-end ditag (PET) sequencing identified 542 functional p53 binding sites...

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“…The most down-regulated transcript in our data set, zinc finger and BTB domain-containing protein 16 (ZBTB16) was originally identified as a fusion partner of the retinoic acid receptor α (RARα) in acute promyeloid leukemia (Chen et al, 1993). ZBTB16 is a member of the promyelocytic leukemia zinc finger (PLZF) family of which factors are shown to be critically involved in the hematopoietic differentiation acting as sequence-specific silencers of gene expression (Siggs and Beutler, 2012). In our data set, we have 4 dysregulated members of PLZF family indicating that chronic TCDD exposure in our model was associated with profound transcriptional remodeling, consistent with the growing realization of the AhR involvement in the wide scale epigenetic remodeling (Tian, 2009).…”

Section: Discussionmentioning

confidence: 99%

Chronic TCDD exposure results in the dysregulation of gene expression in splenic B-lymphocytes and in the impairments in T-cell and B-cell differentiation in mouse model

Tian

Krylova

et al. 2016

Journal of Environmental Sciences

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The BTB-ZF transcription factors

Cited by 121 publications

References 137 publications

MAZR and Runx Factors Synergistically Repress ThPOK during CD8+ T Cell Lineage Development

MAZR and Runx Factors Synergistically Repress ThPOK during CD8+ T Cell Lineage Development

PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function

Chronic TCDD exposure results in the dysregulation of gene expression in splenic B-lymphocytes and in the impairments in T-cell and B-cell differentiation in mouse model

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