Functional Mapping of the GAGA Factor Assigns Its Transcriptional Activity to the C-terminal Glutamine-rich Domain

Vaquero, Alejandro; Espinás, Maria Lluı̈sa; Azorı́n, Fernando; Bernués, Jordi

doi:10.1074/jbc.m000967200

Cited by 32 publications

(25 citation statements)

References 35 publications

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“…It was shown earlier that the C-terminal glutamine-rich domain of GAGA is essential for GAGA-dependent activation both in vitro and in vivo (4). However, the results reported here show that, in addition, the POZ/BTB domain also appeared to have a direct contribution to activation because ⌬POZ GAGA did not efficiently activate the eve promoter.…”

Section: Figcontrasting

confidence: 55%

“…Many developmentally regulated genes in Drosophila are known to be activated by GAGA (1), and it has been shown that GAGA acts as a transcription activator in vitro or upon transient transfection in cultured S2 cells (2)(3)(4). On the other hand, at the preblastoderm stage, TTK acts as a maternally provided repressor of several pair-rule genes that was proposed to contribute to the establishment of the precise timing of their zygotic expression (5)(6)(7).…”

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confidence: 99%

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Repression by TTK69 of GAGA-mediated Activation Occurs in the Absence of TTK69 Binding to DNA and Solely Requires the Contribution of the POZ/BTB Domain of TTK69

Pagans

Piñeyro²,

Kosoy³

et al. 2004

Journal of Biological Chemistry

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tramtrack 69 (TTK69) is known to repress GAGA-mediated activation of the eve promoter in S2 cells. Here, we show that repression by TTK69 occurs in the absence of bona fide TTK69-binding sites on the template, indicating that it does not require the binding of TTK69 to DNA. Consistent with this interpretation, the POZ/BTB domain of TTK69, which does not bind DNA, is sufficient for repression. Moreover, a fusion protein in which the POZ/BTB domain of GAGA is replaced by that of TTK69 is not capable of activating the eve promoter but efficiently represses GAGA-dependent activation. Repression involves GAGA-TTK69 interaction because TTK69 is not capable of repressing basal transcription. Most probably, GAGA-TTK69 interaction occurs at the promoter because GAGA⅐TTK69 complexes are fully competent in binding DNA in vitro. Our results also show that repression by TTK69 of GAGA-dependent activation of the eve promoter is not mediated by any of the co-repressors known to interact with TTK69 (dMi2 or C-terminal binding protein) or by trichostatin A-sensitive histone deacetylases. Altogether, these observations strongly suggest that the binding of TTK69 prevents the interaction of GAGA with the transcription machinery and, therefore, compromises its activation potential.

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Section: Figcontrasting

confidence: 55%

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confidence: 99%

Repression by TTK69 of GAGA-mediated Activation Occurs in the Absence of TTK69 Binding to DNA and Solely Requires the Contribution of the POZ/BTB Domain of TTK69

Pagans

Piñeyro²,

Kosoy³

et al. 2004

Journal of Biological Chemistry

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“…sistent with the proposal that GAGA factor interactions with GAGAG sites 1 and 2 play an important role in other proteins, including several that have BTB/POZ domains and/or interact with DNA (Espinas et al 2000; Fab-7 boundary activity in early embryos. Unfortunately, in the absence of a sensitized assay system it is not possi- Pointud et al 2001;Pagans et al 2002;Faucheux et al 2003;Mishra et al 2003).…”

Section: R67mentioning

confidence: 95%

The Enhancer-Blocking Activity of the Fab-7 Boundary From the Drosophila Bithorax Complex Requires GAGA-Factor-Binding Sites

et al. 2004

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In the work reported here we have analyzed the role of the GAGA factor [encoded by the Trithorax-like (Trl) gene] in the enhancer-blocking activity of Frontabdominal-7 (Fab-7), a domain boundary element from the Drosophila melanogaster bithorax complex (BX-C). One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin. GAGA protein has been shown to localize to the Fab-7 boundary in vivo, and we show that it recognizes sequences from HS1 in vitro. Using two different transgene assays we demonstrate that GAGA-factor-binding sites are necessary but not sufficient for full Fab-7 enhancer-blocking activity. We show that distinct GAGA sites are required for different enhancer-blocking activities at different stages of development. We also show that the enhancer-blocking activity of the endogenous Fab-7 boundary is sensitive to mutations in the gene encoding the GAGA factor Trithorax-like.

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“…BACK domains are typically found immediately following the BTB domain in BTB-Kelch proteins but their function is still unclear (Stogios and Privé 2004). Polyglutamine domains are found in several transcriptional regulators including the BTB-zinc finger protein GAGA in which it acts as a transactivation domain (Vaquero et al 2000). It is not yet clear whether EOR-1 functions as a transcriptional repressor and/or activator, as none of its direct targets are known.…”

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EOR-2 Is an Obligate Binding Partner of the BTB–Zinc Finger Protein EOR-1 in Caenorhabditis elegans

et al. 2010

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BTB-zinc finger transcription factors play many important roles in metazoan development. In these proteins, the BTB domain is critical for dimerization and for recruiting cofactors to target genes. Identification of these cofactors is important for understanding how BTB-zinc finger proteins influence transcription. Here we show that the novel but conserved protein EOR-2 is an obligate binding partner of the BTB-zinc finger protein EOR-1 in Caenorhabditis elegans. EOR-1 and EOR-2 function together to promote multiple Ras/ERK-dependent cell fates during development, and we show that EOR-1 is a robust substrate of ERK in vitro. A point mutation (L81F) in the EOR-1 BTB domain reduces both ERK phosphorylation and EOR-2 binding and eliminates all detectable biological function without affecting EOR-1 expression levels, localization, or dimerization. This point mutation lies near the predicted charged pocket region of the EOR-1 BTB dimer, a region that, in other BTB-zinc finger proteins, has been proposed to interact with corepressors or coactivators. We also show that a conserved zinc finger-like motif in EOR-2 is required for binding to EOR-1, that the interaction between EOR-1 and EOR-2 is direct, and that EOR-2 can bind to the human BTB-zinc finger protein PLZF. We propose that EOR-2 defines a new family of cofactors for BTB-zinc finger transcription factors that may have conserved roles in other organisms.

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Functional Mapping of the GAGA Factor Assigns Its Transcriptional Activity to the C-terminal Glutamine-rich Domain

Cited by 32 publications

References 35 publications

Repression by TTK69 of GAGA-mediated Activation Occurs in the Absence of TTK69 Binding to DNA and Solely Requires the Contribution of the POZ/BTB Domain of TTK69

Repression by TTK69 of GAGA-mediated Activation Occurs in the Absence of TTK69 Binding to DNA and Solely Requires the Contribution of the POZ/BTB Domain of TTK69

The Enhancer-Blocking Activity of the Fab-7 Boundary From the Drosophila Bithorax Complex Requires GAGA-Factor-Binding Sites

EOR-2 Is an Obligate Binding Partner of the BTB–Zinc Finger Protein EOR-1 in Caenorhabditis elegans

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