Transcriptional regulation of the <i>Drosophila ANT</i> gene by the DRE/DREF system

Kim, Young S.; Shin, Meong Joo; Yang, Dong; Yamaguchi, Masamitsu; Park, So Young; Yoo, Mi‐Ae

doi:10.1111/j.1365-2443.2007.01075.x

Cited by 10 publications

(9 citation statements)

References 49 publications

(43 reference statements)

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“…We first examined two independent lines that each contained a P-element insertion within the 5 0 region of the dref locus (dref KG09294 and dref NP4719 ). A previous report showed that the dref KG09294 flies had markedly reduced dref mRNA levels (Kim et al, 2007). We also observed that dref KG09294 cell clones in the mitotic larval wing disc show little or no DREF protein (Fig.…”

Section: Dref Is Required For Cellular and Organismal Growth In Drososupporting

confidence: 78%

DREF is required for cell and organismal growth in Drosophila and functions downstream of the nutrition/TOR pathway

Killip

Grewal

2012

Developmental Biology

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Nutrient availability is a key determinant of animal growth. The conserved insulin/PI3 kinase and TOR kinase signaling pathways are two of the best characterized regulators of cell and tissue growth in response to nutritional conditions. Studies in Drosophila larvae show that one mechanism by which these pathways drive growth is by regulating the expression of metabolic genes, especially those genes required for protein synthesis. Here we examine a role for the transcription factor DREF in mediating some of these transcriptional and growth responses. We find that loss of DREF leads to a decrease in organismal growth. These effects are in part due to a requirement for DREF function in cell-autonomous growth. We also uncover a non-autonomous role for DREF activity in the larval fat body. Previous studies show that activation of TOR in the fat body couples nutrition to insulin release from the brain; we find that inhibition of DREF in the fat body can phenocopy effects of nutrient deprivation and fat-specific TOR inhibition, leading to a reduction in systemic insulin signaling, delayed larval growth and smaller final size. Using genetic epistasis, we find that DREF is required for growth downstream of TOR, but not insulin/PI3K signaling. Moreover, we show that TOR can control DREF mRNA levels, in part via the transcription factor dMyc. Finally we show that DREF is required for normal expression of many ribosome biogenesis genes, suggesting that one mechanism by which DREF is required for growth is through the control of protein synthetic capacity. Together these findings suggest DREF is an essential transcription factor in the nutritional control of cell and tissue growth during Drosophila development. Given that DREF is conserved, this role may also be important in the control of growth in other animals.

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Section: Dref Is Required For Cellular and Organismal Growth In Drososupporting

confidence: 78%

DREF is required for cell and organismal growth in Drosophila and functions downstream of the nutrition/TOR pathway

Killip

Grewal

2012

Developmental Biology

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“…For this purpose, we carried out lacZ staining of both initial and flipped out lines of ME boundary in the Dref mutant background. We did not find any effect of Dref KG09294 on ME boundary although this allele is known to affect the function of this protein (61), (Supplementary Figure S6). We, therefore, conclude that ME boundary function is not affected by Dref and that the BEAF recognition motif present in ME boundary responds only to BEAF.…”

Section: Resultsmentioning

confidence: 82%

A BEAF dependent chromatin domain boundary separates myoglianin and eyeless genes of Drosophila melanogaster

Sultana

Verma

Mishra

2011

Nucleic Acids Research

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Precise transcriptional control is dependent on specific interactions of a number of regulatory elements such as promoters, enhancers and silencers. Several studies indicate that the genome in higher eukaryotes is divided into chromatin domains with functional autonomy. Chromatin domain boundaries are a class of regulatory elements that restrict enhancers to interact with appropriate promoters and prevent misregulation of genes. While several boundary elements have been identified, a rational approach to search for such elements is lacking. With a view to identifying new chromatin domain boundary elements we analyzed genomic regions between closely spaced but differentially expressed genes of Drosophila melanogaster. We have identified a new boundary element between myoglianin and eyeless, ME boundary, that separates these two differentially expressed genes. ME boundary maps to a DNaseI hypersensitive site and acts as an enhancer blocker both in embryonic and adult stages in transgenic context. We also report that BEAF and GAF are the two major proteins responsible for the ME boundary function. Our studies demonstrate a rational approach to search for potential boundaries in genomic regions that are well annotated.

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“…Why are there two such similar genes? Previously ANT-lacZ transgenic flies were shown to express lacZ widely throughout the developmental stages (23); however, recent postgenomic resources allow a more refined view. FlyAtlas, a comprehensive microarray-based atlas of gene expression in multiple Drosophila tissues (8), reports distinct expression patterns for sesB and ANT2 genes (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Mislocalization of mitochondria and compromised renal function and oxidative stress resistance inDrosophila SesBmutants

Terhzaz

Cabrero

Chintapalli

et al. 2010

Physiological Genomics

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Terhzaz S, Cabrero P, Chintapalli VR, Davies S, Dow JAT. Mislocalization of mitochondria and compromised renal function and oxidative stress resistance in Drosophila SesB mutants. Physiol Genomics 41: 33-41, 2010. First published December 15, 2009 doi:10.1152/physiolgenomics.00147.2009.-Mitochondria accumulate at sites of intense metabolic activity within cells, but the adaptive value of this placement is not clear. In Drosophila, sesB encodes the ubiquitous isoform of adenine nucleotide translocase (ANT, the mitochondrial inner membrane ATP/ADP exchanger); null alleles are lethal, whereas hypomorphic alleles display sensitivity to a range of stressors. In the adult renal tubule, which is densely packed with mitochondria and hence enriched for sesB, both hypomorphic alleles and RNA interference knockdowns cause the mitochondria to lose their highly polarized distribution in the tissue and to become rounded. Basal cytoplasmic and mitochondrial calcium levels are both increased, and neuropeptide calcium response compromised, with concomitant defects in fluid secretion. The remaining mitochondria in sesB mutants are overactive and maintain depleted cellular ATP levels while generating higher levels of hydrogen peroxide than normal. When sesB expression is knocked down in just tubule principal cells, the survival of the whole organism upon oxidative stress is reduced, implying a limiting role for the tubule in homeostatic response to stressors. The physiological impacts of defective ANT expression are thus widespread and diverse. Drosophila melanogaster; Malpighian tubule; adenine nucleotide translocase; mitochondria MITOCHONDRIA ARE ESSENTIAL organelles for the function of all aerobic cells, as they produce ATP, buffer cytosolic calcium, and sequester apoptotic factors. Impairment of mitochondrial function, resulting in excitotoxic metabolic insufficiency, cell death, and oxidative damage, can contribute to severe tissue pathologies and diseases (36,44). Mitochondria are also highly dynamic, and accumulate at sites with particularly high ATP consumption (3,13,17,31,37).The mitochondrial adenine nucleotide translocase (ANT) is the most abundant protein of the inner mitochondrial membrane and a crucial component in the maintenance of cellular energy homeostasis, as well as in the formation of the mitochondrial permeability transition pore (2, 15). It catalyzes ADP/ATP exchange across the mitochondrial inner membrane (24) and thus has the potential to allow mitochondrial sensing of subcellular ATP:ADP poise. ANT is a target of oxidative damage, and functional inactivation has been associated with chronological age as well as physiological age (51). In mammals, the majority of species, including humans, possess three distinct genes for ANT (9,25,26,28). Drosophila harbors two overlapping ANT genes, ANT1 (sesB), and ANT2, with 72% nucleotide identity with 78% amino acid sequence identity (52). Mutations affecting ANT1 in Drosophila were originally identified as a stress-sensitive strain of animals (sesB) that are condi...

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Transcriptional regulation of the Drosophila ANT gene by the DRE/DREF system

Cited by 10 publications

References 49 publications

DREF is required for cell and organismal growth in Drosophila and functions downstream of the nutrition/TOR pathway

DREF is required for cell and organismal growth in Drosophila and functions downstream of the nutrition/TOR pathway

A BEAF dependent chromatin domain boundary separates myoglianin and eyeless genes of Drosophila melanogaster

Mislocalization of mitochondria and compromised renal function and oxidative stress resistance inDrosophila SesBmutants

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