A Functionally Conserved N-terminal Domain of the Friend of GATA-2 (FOG-2) Protein Represses GATA4-Dependent Transcription

Svensson, E. C.; Huggins, Gordon S.; Dardik, Fred B.; Polk, Christine E.; Leiden, Jeffrey M.

doi:10.1074/jbc.m001522200

Cited by 111 publications

(121 citation statements)

References 38 publications

(59 reference statements)

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“…We have previously shown that multiple zinc fingers domains of FOG-2 are able to physically associate with the N-terminal zinc finger of GATA4 [16]. Since the zinc finger domains of FOG-2 and FOG-2S are identical, we would predict that FOG-2S would be able to bind GATA4.…”

Section: Fog-2s Physically Interacts With Gata4mentioning

confidence: 96%

“…This protein is identical to FOG-2 except it lacks the N-terminal 132 amino acids where the FOG repression motif is located (Figure 1). It contains all of the zinc finger motifs, the C-terminal binding protein (CtBP) interaction domain, and the nuclear localization domain previously characterized in FOG-2 [16].…”

Section: Isolation Of An Alternative Transcript Of Murine Fog-2mentioning

confidence: 99%

“…This interaction is mediated by multiple zinc fingers of the FOG proteins and the N-terminal zinc finger of the GATA factors [9][10][11][12][13]. In most cell and promoter contexts examined to date, this interaction results in the repression of GATA-mediated transactivation of target promoters [14][15][16][17][18][19]. There are two potential domains of FOG proteins that may mediate transcriptional repression.…”

Section: Introductionmentioning

confidence: 99%

“…The first is a domain in the C-terminal portion of both FOG-1 and FOG-2 that contains a consensus binding site for C-terminal Binding Protein (CtBP), a transcriptional co-repressor family [20]. Both FOG-1 and FOG-2 have been shown to interact with CtBP-2, but the functional significance of this interaction is unclear, as disruption or deletion of this site in vitro or in vivo does not affect FOG function [9,16,21]. We have previously identified a second domain of FOG proteins localized at the N-terminus of all vertebrate FOG proteins, the FOG repression motif, which is necessary for transcriptional repression [22].…”

Section: Introductionmentioning

confidence: 99%

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An alternative transcript of the FOG-2 gene encodes a FOG-2 isoform lacking the FOG repression motif

Dale

Remo

Svensson

2007

Biochemical and Biophysical Research Communications

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The FOG family of transcriptional co-factors is composed of two members in mammals: FOG-1 and FOG-2. Both have been shown to bind to GATA factors and function as transcriptional co-repressors in specific cell and promoter contexts. We have previously defined a novel repression domain localized to the N-terminus of each FOG family member, the FOG Repression Motif, which is necessary for FOG-mediated transcriptional repression. In this report, we describe the identification and characterization of a novel isoform of FOG-2 lacking the FOG Repression Motif. In contrast to full-length FOG-2, this isoform is expressed predominately in the embryonic and adult heart. It can bind GATA4 avidly, but is unable to repress GATA4-mediated activation of cardiac-restricted gene promoters. Together, these results suggest that FOG-2 repressive activity may be modulated by the generation of isoforms of FOG-2 lacking the FOG repression motif.

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Section: Fog-2s Physically Interacts With Gata4mentioning

confidence: 96%

Section: Isolation Of An Alternative Transcript Of Murine Fog-2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An alternative transcript of the FOG-2 gene encodes a FOG-2 isoform lacking the FOG repression motif

Dale

Remo

Svensson

2007

Biochemical and Biophysical Research Communications

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“…Second, FOG-1 might endow GATA-1 with corepressor activity. In support of the latter possibility, it has been shown that FOG proteins can associate with members of the carboxyl-terminal binding protein (CtBP) family of corepressors (7,(39)(40)(41)(42), although the relevance of these interactions to erythroid gene expression remains uncertain (43). To distinguish between these two possibilities, we examined occupancy by wild-type and mutant GATA-1-ER protein at the GATA-2 gene.…”

Section: Hs2 (mentioning

confidence: 99%

Context-dependent regulation of GATA-1 by friend of GATA-1

Letting

Chen²,

Rakowski³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

126

134

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The transcription factor GATA-1 and its cofactor, friend of GATA-1 (FOG-1), are essential for normal erythroid development. FOG-1 physically interacts with GATA-1 to augment or inhibit its activity. The mechanisms by which FOG-1 regulates GATA-1 function are unknown. By using an assay that is based on the phenotypic rescue of a GATA-1-null erythroid cell line, we found that a conditional form of GATA-1 (GATA-1-ER) strongly induced histone acetylation at the ␤-major globin promoter in vivo, consistent with previous results. In contrast, GATA-1 bearing a point mutation that impairs FOG-1 binding [GATA-1(V205M)-ER] failed to induce high levels of histone acetylation at this site. However, at DNase I-hypersensitive site (HS)3 of the ␤-globin locus control region, GATA-1-induced histone acetylation was FOG-1-independent. Because the V205M mutation does not disrupt GATA-1 binding to DNA templates in vitro, we were surprised to find that in vivo GATA-1(V205M)-ER fails to bind the ␤-globin promoter. However, at HS3, DNA binding by GATA-1 was FOG-1-independent, thus correlating histone acetylation with GATA-1 occupancy. Examination of additional GATA-1-dependent regulatory elements showed that the interaction with FOG-1 is required for GATA-1 occupancy at select sites, such as HS2, but is dispensable at others, including the FOG-1-independent GATA-1 target gene EKLF. Remarkably, at the GATA-2 gene, which is repressed by GATA-1, interaction with FOG-1 was dispensable for GATA-1 occupancy and was required for transcriptional inhibition and histone deacetylation. These results indicate that FOG-1 employs distinct mechanisms when cooperating with GATA-1 during transcriptional activation and repression.globin ͉ chromatin ͉ histones ͉ acetylation

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The Role of the Transcriptional Corepressor FOG‐2 in Cardiac Development

Svensson¹,

Wilk²,

Dale³

et al. 2005

Cardiovascular Development and Congenital Malformations

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A Functionally Conserved N-terminal Domain of the Friend of GATA-2 (FOG-2) Protein Represses GATA4-Dependent Transcription

Abstract: GATA4 isTaken together, these results define a set of evolutionarily conserved mechanisms by which FOG proteins repress GATA-dependent transcription and thereby form the foundation for genetic studies designed to elucidate the role of FOG-2 in cardiac development.

Cited by 111 publications

References 38 publications

An alternative transcript of the FOG-2 gene encodes a FOG-2 isoform lacking the FOG repression motif

An alternative transcript of the FOG-2 gene encodes a FOG-2 isoform lacking the FOG repression motif

Context-dependent regulation of GATA-1 by friend of GATA-1

The Role of the Transcriptional Corepressor FOG‐2 in Cardiac Development

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