GATA Transcription Factor Required for Immunity to Bacterial and Fungal Pathogens

Abstract NG-monomethyl-l-arginine (L-NMMA) has been reported to be elevated in uremic patients. Based on the hypothesis that the pathogenesis of the anemia of renal disease might be due to the perturbation of transcription factors of the erythropoietin (Epo) gene by L-NMMA, the present study was designed to investigate the effect of L-NMMA on Epo gene expression through the GATA transcription factor. L-NMMA caused decreased levels of NO, cyclic guanosine monophosphate (cGMP), and Epo protein in Hep3B cells. L-NAME (analogue of L-NMMA) also inhibited Epo production in anemic mice. Transfection of the Epo promoter-luciferase gene into Hep3B cells revealed that L-NMMA inhibited the Epo promoter activity. However, L-NMMA did not inhibit the Epo promoter activity when mutated Epo promoter (GATA to TATA) was transfected, and L-NMMA did not affect the enhancer activity. Electrophoretic mobility shift assays demonstrated the stimulation of GATA binding activity by L-NMMA. However, L-NMMA had no effect on the binding activity of hepatic nuclear factor-4, COUP-TF1, hypoxia-inducing factor-1, or NF-κB. Furthermore, cGMP inhibited the L-NMMA–induced GATA binding activity. L-NMMA also increased GATA-2 messenger RNA expression. These results demonstrate that L-NMMA suppresses Epo gene expression by up-regulation of the GATA transcription factor and support the hypothesis that L-NMMA is one of the candidate substances that underlie the pathogenesis of renal anemia.

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Ectopic expression of a Haemonchus contortus GATA transcription factor in Caenorhabditis elegans reveals conserved function in spite of extensive sequence divergence

Molecular and Biochemical Parasitology ◽

10.1016/j.molbiopara.2003.10.012 ◽

2004 ◽

Vol 133 (2) ◽

pp. 241-253 ◽

Cited By ~ 36

Author(s):

Annabelle Couthier ◽

Judith Smith ◽

Pamela McGarr ◽

Barbara Craig ◽

John S Gilleard

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Haemonchus Contortus ◽

Ectopic Expression ◽

Sequence Divergence ◽

Extensive Sequence ◽

Gata Transcription Factor

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TORC1 Regulates Developmental Responses to Nitrogen Stress via Regulation of the GATA Transcription Factor Gaf1

mBio ◽

10.1128/mbio.00959-15 ◽

2015 ◽

Vol 6 (4) ◽

Cited By ~ 18

Author(s):

Dana Laor ◽

Adiel Cohen ◽

Martin Kupiec ◽

Ronit Weisman

Keyword(s):

Transcription Factor ◽

Sexual Development ◽

Nitrogen Availability ◽

Stress Conditions ◽

Nitrogen Stress ◽

Content Type ◽

Downstream Target ◽

Gata Transcription Factor ◽

Novel Target ◽

Developmental Responses

ABSTRACT The TOR (target of rapamycin [sirolimus]) is a universally conserved kinase that couples nutrient availability to cell growth. TOR complex 1 (TORC1) in Schizosaccharomyces pombe positively regulates growth in response to nitrogen availability while suppressing cellular responses to nitrogen stress. Here we report the identification of the GATA transcription factor Gaf1 as a positive regulator of the nitrogen stress-induced gene isp7 +, via three canonical GATA motifs. We show that under nitrogen-rich conditions, TORC1 positively regulates the phosphorylation and cytoplasmic retention of Gaf1 via the PP2A-like phosphatase Ppe1. Under nitrogen stress conditions when TORC1 is inactivated, Gaf1 becomes dephosphorylated and enters the nucleus. Gaf1 was recently shown to negatively regulate the transcription induction of ste11 +, a major regulator of sexual development. Our findings support a model of a two-faceted role of Gaf1 during nitrogen stress. Gaf1 positively regulates genes that are induced early in the response to nitrogen stress, while inhibiting later responses, such as sexual development. Taking these results together, we identify Gaf1 as a novel target for TORC1 signaling and a step-like mechanism to modulate the nitrogen stress response. IMPORTANCE TOR complex 1 (TORC1) is an evolutionary conserved protein complex that positively regulates growth and proliferation, while inhibiting starvation responses. In fission yeast, the activity of TORC1 is downregulated in response to nitrogen starvation, and cells reprogram their transcriptional profile and prepare for sexual development. We identify Gaf1, a GATA-like transcription factor that regulates transcription and sexual development in response to starvation, as a downstream target for TORC1 signaling. Under nitrogen-rich conditions, TORC1 positively regulates the phosphorylation and cytoplasmic retention of Gaf1 via the PP2A-like phosphatase Ppe1. Under nitrogen stress conditions when TORC1 is inactivated, Gaf1 becomes dephosphorylated and enters the nucleus. Budding yeast TORC1 regulates GATA transcription factors via the phosphatase Sit4, a structural homologue of Ppe1. Thus, the TORC1-GATA transcription module appears to be conserved in evolution and may also be found in higher eukaryotes.

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