BAZF, a Novel Bcl6 Homolog, Functions as a Transcriptional Repressor

Okabe, Shinichiro; Fukuda, Tetsuya; Ishibashi, Ko; Kojima, Satoko; Okada, Seiji; Hatano, Masahiko; Ebara, Masaaki; Saisho, Hiromitsu; Tokuhisa, Takeshi

doi:10.1128/mcb.18.7.4235

Cited by 77 publications

(65 citation statements)

References 41 publications

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“…Consistent with the enhancer function of the E-box element (86), ZENON strongly induces TH promoter activity in a cell line. This finding is in contrast to the transcriptional repression by the POZ domain reported for most POZ proteins (32,38,43,45,58). The ZENON POZ domain includes serine at a key position at which lysine or arginine is usually found.…”

Section: Discussioncontrasting

confidence: 77%

“…This model involves oligomerization through the POZ domain and suggests a key role for the POZ domain in selecting the target genes regulated by GAGA (35). POZ factors often contain other transcriptional regulation domains outside the POZ domain (45,52,58). The activation of transcription by ZENON is probably mediated by another domain, possibly located in the C-terminal part of the protein, because the removal of this part substantially reduced the induction of TH promoter activity.…”

Section: Discussionmentioning

confidence: 99%

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ZENON, a Novel POZ Kruppel-Like DNA Binding Protein Associated with Differentiation and/or Survival of Late Postmitotic Neurons

Kiefer

Chatail-Hermitte

Ravassard

et al. 2005

Molecular and Cellular Biology

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The rat tyrosine hydroxylase gene promoter contains an E-box/dyad motif and an octameric and heptameric element that may be recognized by classes of transcription factors highly expressed during nervous system development. In a one-hybrid genetic screen, we used these sites as targets to isolate cDNAs encoding new transcription factors present in the brain. We identified ZENON, a novel rat POZ protein that contains two clusters of Kruppel-like zinc fingers and that presents several features of a transcription factor. ZENON is found in nuclei following transient transfection with the cDNA. The N-terminal zinc finger cluster contains a DNA binding domain that interacts with the E box. Cotranfection experiments revealed that ZENON induces tyrosine hydroxylase promoter activity. Unlike other POZ proteins, the ZENON POZ domain is not required for either activation of transcription or self-association. In the embryonic neural tube, ZENON expression is restricted to neurons that have already achieved mitosis and are engaged in late stages of neuronal differentiation (late postmitotic neurons). ZENON neuronal expression persists in the adult brain; therefore, ZENON can be considered a marker of mature neurons. We propose that ZENON is involved in the maintenance of panneuronal features and/or in the survival of mature neurons.The two major cell types in the nervous system, neurons and glia, both comprise a large number of subtypes. The generation and maintenance of this phenotypic diversity require extracellular signals that are converted into tightly regulated transcriptional cascades. Many transcription factors involved in these cascades-often basic helix-loop-helix (bHLH), homeodomain, or zinc finger-containing proteins-remain to be identified. Description of these factors would help elucidate the molecular events leading to the differentiation of the various cell types in the nervous system.One way to identify these factors is to isolate novel proteins that interact with sequences promoting the neural expression of a highly developmentally regulated gene. A good candidate is the gene encoding tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis (44, 56). The expression of the TH gene is a common feature of all neurons and neuroendocrine cells that synthesize and release catecholamines (dopamine, norepinephrine, and epinephrine). These cells are extremely diverse in their functional, morphological, and anatomical properties and have different embryonic origins. Depending on their locations in the adult central nervous system (CNS) and peripheral nervous system (PNS), catecholaminergic cells originate from different parts of the neural tube and neural crest (6,73,74). In the embryonic neural tube, catecholaminergic cell groups arise from various neuromeres (64, 78), suggesting that a large number of extracellular signals and transcription factors govern the specification and maintenance of catecholaminergic identity.The production and functional analysis of knockout mice revealed the essen...

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Section: Discussioncontrasting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

ZENON, a Novel POZ Kruppel-Like DNA Binding Protein Associated with Differentiation and/or Survival of Late Postmitotic Neurons

Kiefer

Chatail-Hermitte

Ravassard

et al. 2005

Molecular and Cellular Biology

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“…The N-terminal region of HOF contains a BTB/POZ domain that has about 36% overall amino acid homology to the BTB/ POZ domains of BCL-6, a potential oncogene involved in chromosomal translocations in a third of diffuse large cell lymphomas (15); BAZF, which is a BCL-6 homologous gene of unknown function (16); PLZF, whose chromosomal translocation is involved in acute promyelocytic leukemia (17); and Miz-1, a c-Myc-interacting protein containing 13 C 2 H 2 zinc fingers (18) (Fig. 1C).…”

Section: Methodsmentioning

confidence: 99%

Characterization of Two Novel Nuclear BTB/POZ Domain Zinc Finger Isoforms

Mitchelmore¹,

Kjærulff²,

Pedersen³

et al. 2002

Journal of Biological Chemistry

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BTB/POZ (broad complex tramtrack bric-a-brac/poxvirus and zinc finger) zinc finger factors are a class of nuclear DNA-binding proteins involved in development, chromatin remodeling, and cancer. However, BTB/POZ domain zinc finger factors linked to development of the mammalian cerebral cortex, cerebellum, and macroglia have not been described previously. We report here the isolation and characterization of two novel nuclear BTB/POZ domain zinc finger isoforms, designated HOF L and HOF S , that are specifically expressed in early hippocampal neurons, cerebellar granule cells, and gliogenic progenitors as well as in differentiated glia. During embryonic development of the murine cerebral cortex, HOF expression is restricted to the hippocampal subdivision. Expression coincides with early differentiation of presumptive CA1 and CA3 pyramidal neurons and dentate gyrus granule cells, with a sharp decline in expression at the CA1/subicular border. By using bromodeoxyuridine labeling and immunohistochemistry, we show that HOF expression coincides with immature non-dividing cells and is down-regulated in differentiated cells, suggesting a role for HOF in hippocampal neurogenesis. Consistent with the postulated role of the POZ domain as a site for protein-protein interactions, both HOF isoforms are able to dimerize. The HOF zinc fingers bind specifically to the binding site for the related promyelocytic leukemia zinc finger protein as well as to a newly identified DNA sequence.

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“…BCL6 harbors two separable transrepressing regions: the ®rst one is the Nterminal and self-interacting domain, termed POZ (or BTB), which is conserved in many metazoan zinc ®nger or actin-binding proteins; the other one encompasses a large central part of the protein and contains a short sequence shared by the BCL6 close relative BAZF (Bardwell and Treisman, 1994;Albagli et al, 1995Albagli et al, , 1996Chang et al, 1996;Seyfert et al, 1996;Baron et al, 1997;Okabe et al, 1998). The center of the latter region is subjected to phosphorylation by MAPK kinase on two nearby sites, an event that triggers the ubiquitin/proteasome dependent degradation of the BCL6 protein Niu et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Overexpressed BCL6 (LAZ3) oncoprotein triggers apoptosis, delays S phase progression and associates with replication foci

et al. 1999

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One of the most frequent genetic abnormalities associated with non Hodgkin lymphoma is the structural alteration of the 5' non coding/regulatory region of the BCL6 (LAZ3) protooncogene. BCL6 encodes a POZ/ Zn ®nger protein, a structure similar to that of many Drosophila developmental regulators and to another protein involved in a human hematopoietic malignancy, PLZF. BCL6 is a sequence speci®c transcriptional repressor controlling germinal center formation and T cell dependent immune response. Although the expression of BCL6 negatively correlates with cellular proliferation in di erent cell types, the in¯uence of BCL6 on cell growth and survival is currently unknown so that the way its deregulation may contribute to cancer remains elusive. To directly address this issue, we used a tetracycline-regulated system in human U2OS osteosarcoma cells and thus found that BCL6 mediates growth suppression associated with impaired S phase progression and apoptosis. Interestingly, overexpressed BCL6 can colocalize with sites of ongoing DNA synthesis, suggesting that it may directly interfere with S phase initiation and/or progression. In contrast, the isolated Zn ®nger region of BCL6, which binds BCL6 target sequence but lacks transcriptional repression activity, slows, but does not suppress, U2OS cell growth, is less e cient at delaying S phase progression, and does not trigger apoptosis. Thus, for a large part, the e ects of BCL6 overexpression on cell growth and survival depend on its ability to engage protein/protein interactions with itself and/or its transcriptional corepressors. That BCL6 restricts cell growth suggests that its deregulation upon structural alterations may alleviate negative controls on the cell cycle and cell survival.

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BAZF, a Novel Bcl6 Homolog, Functions as a Transcriptional Repressor

Cited by 77 publications

References 41 publications

ZENON, a Novel POZ Kruppel-Like DNA Binding Protein Associated with Differentiation and/or Survival of Late Postmitotic Neurons

ZENON, a Novel POZ Kruppel-Like DNA Binding Protein Associated with Differentiation and/or Survival of Late Postmitotic Neurons

Characterization of Two Novel Nuclear BTB/POZ Domain Zinc Finger Isoforms

Overexpressed BCL6 (LAZ3) oncoprotein triggers apoptosis, delays S phase progression and associates with replication foci

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