Both upstream and intron sequence elements are required for elevated expression of the rat somatic cytochrome c gene in COS-1 cells.

Evans, Mark J.; Scarpulla, Richard C.

doi:10.1128/mcb.8.1.35

Cited by 75 publications

(40 citation statements)

References 48 publications

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“…Studies of the RC4 promoter have revealed multiple control regions both upstream and within the first intron (Evans andScarpulla 1988a, 1989). Some of these regions are the targets for nuclear factors, such as ATF (Lin and Green 1988) and Spl (Briggs et al 1986), which also activate many other unrelated genes.…”

Section: Discussionmentioning

confidence: 99%

“…Rat and human cytochrome c genes were initially isolated to serve as a model system to investigate the regulation of nuclear genes encoding mitochondrial respiratory functions in animal cells (Scarpulla 1984;Evans and Scarpulla 1988b;Virbasius and Scarpulla 1988). Studies of the RC4 promoter have revealed multiple control regions both upstream and within the first intron (Evans andScarpulla 1988a, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, the formation of the NRF-1 complex was not inhibited by an excess of plasmids containing either the RC4 ATF transcription factor-binding site (RC4 -281/-256, lanes 3 and 14), or RC4 promoter region I (RC4 -187/-161, lanes 11 and 22). The latter is an independent cis-acting promoter element for which a trans-acting factor has yet to be identified (Evans andScarpulla 1988a, 1989). In contrast, NRF-1 complex formation was strongly inhibited when the binding reactions contained an excess of cloned rat (RC4 -172/-147, lanes 4 and 15) or human (HCS -171/-154, lanes 5 and 16) cytochrome c NRF-1 sequences.…”

Section: Nrf-1 Recognition Sites Are Common To Nuclear Genes Whose Prmentioning

confidence: 99%

“…Comparison of NRF-l-binding site similarities in several nuclear genes encoding mitochondrial functions. Sequences from the HCS gene (Evans and Scarpulla 1988b), the COX-VIc-2 gene (Suske et al 1988), the hCC 1 gene (Suzuki et al 1989a), the hQP gene (Suzuki et al 1989b), and the mouse (Chang and Clayton 1989) and human (Topper and Clayton 1990) MRP RNA genes are aligned for maximum identity with the RC4 gene NRF-1-binding site. The position of the sequence is indicated relative to the defined transcription start sites for the HCS, COX-VIc-2, and MRP RNA genes.…”

Section: Nrf-1 Recognition Sites Are Common To Nuclear Genes Whose Prmentioning

confidence: 99%

“…To begin to identify transcriptional activators specifically involved in coordinating the expression of nuclear respiratory genes in animal cells, the human and rat cytochrome c genes were isolated (Scarpulla 1984;Evans and Scarpulla 1988b;Virbasius and Scarpulla 1988) and an analysis of the rat somatic cytochrome c (RC4) promoter was performed (Evans andScarpulla 1988a, 1989). One class of promoter sequences identified by mutational mapping and DNase I footprinting is recognized by nuclear factors common to many nonrespiratory genes.…”

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confidence: 99%

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NRF-1: a trans-activator of nuclear-encoded respiratory genes in animal cells.

Evans¹,

Scarpulla²

1990

Genes Dev.

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378

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The assembly of the respiratory apparatus requires the coordinate expression of a large number of genes from both nuclear and mitochondrial genetic systems. In vertebrate organisms, the molecular mechanisms integrating the activities of these distinct genomic compartments in response to tissue demands for respiratory energy remain unknown. A potential inroad to this problem came with the discovery of nuclear respiratory factor 1 (NRF-1), a novel transcriptional activator defined by mutational and DNA binding analysis of the somatic cytochrome c promoter. Functional NRF-1 sites are now observed in several other recently isolated nuclear genes whose products function in the mitochondria. Among these are genes encoding subunits of the cytochrome c oxidase (subunit VIc) and reductase (ubiquinone-binding protein) complexes. In addition, a functional NRF-1 site resides in the MRP RNA gene encoding the RNA moiety of a ribonucleoprotein endonuclease involved in mitochondrial DNA replication. Synthetic oligomers of these sites competitively displace NRF-1 binding to the cytochrome c promoter. NRF-l-binding activities for each site also have the same thermal lability, copurify chromatographically, and make similar guanosine nucleotide contacts within each recognition sequence. Moreover, NRF-1 recognition in vitro correlates with the ability of each site to stimulate expression in vivo from a truncated cytochrome c promoter. The presence of NRF-l-binding sites in nuclear genes encoding structural components of the mammalian electron transport chain, as well as the mitochondrial DNA replication machinery, suggests a mechanism for coordination of nuclear and mitochondrial genetic systems through the concerted modulation of nuclear genes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Nrf-1 Recognition Sites Are Common To Nuclear Genes Whose Prmentioning

confidence: 99%

Section: Nrf-1 Recognition Sites Are Common To Nuclear Genes Whose Prmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

NRF-1: a trans-activator of nuclear-encoded respiratory genes in animal cells.

Evans¹,

Scarpulla²

1990

Genes Dev.

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378

250

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Electron transfer in genetically engineered proteins. The cytochrome c paradigm

Mauk¹

1991

Long-Range Electron Transfer in Biology

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7.3 Transcriptional Integration of Mitochondrial Biogenesis

Scarpulla¹

2007

Handbook of Neurochemistry and Molecular Neurobiology

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Gene regulatory factors encoded by the nuclear genome are essential for mitochondrial biogenesis and function. Some of these factors act exclusively within the mitochondria to regulate the control of mitochondrial transcription, translation and other functions. Others govern the expression of nuclear genes required for mitochondrial metabolism and organelle biogenesis. The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family of transcriptional coactivators plays a major role in transducing and integrating physiological signals governing metabolism, differentiation and cell growth to the transcriptional machinery controlling mitochondrial functional capacity. Thus, the PGC-1 coactivators serve as a central component of the transcriptional regulatory circuitry that coordinately controls the energy-generating functions of mitochondria in accordance with the metabolic demands imposed by changing physiological conditions, senescence, and disease. KeywordsMitochondria; Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1); Peroxisome proliferator-activated receptor (PPAR); transcription; gene regulation; metabolism Regulation of mitochondrial biogenesisA set of nuclear-encoded factors coordinately regulate mitochondrial mass and function in response to a host of energy and growth demands, including cellular metabolic stress, such as the constant production of reactive oxygen species (ROS). Dysregulation of mitochondrial function has broad implications for human disease including diabetes, heart failure and neurodegeneration. Thus, there is a high level of interest in developing therapeutic strategies aimed at modulating the regulatory pathways that control mitochondrial function and biogenesis. The nuclear-encoded transcription factors and coactivators that govern mitochondrial function serve as one major focus. Here we review recent advances in our understanding of this regulatory circuitry and its potential role in integrating mitochondrial biogenesis with cellular stress responses. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The transcription and translation of the mitochondrial genome is dependent upon a host of nuclear-encoded gene products (Figure 1; Box 1). Mitochondrial DNA (mtDNA) transcription requires a single RNA polymerase (POLRMT, see glossary) that shares sequence similarity with yeast mitochondrial and T3/T7 bacteriophage polymerases, two stimulatory transcription factors (Tfam, TFB2M) and a termination factor (MTERF1) [1,2]. Transcription occurs bi-directionally from divergent promoters termed LSP and HSP wi...

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Both upstream and intron sequence elements are required for elevated expression of the rat somatic cytochrome c gene in COS-1 cells.

Cited by 75 publications

References 48 publications

NRF-1: a trans-activator of nuclear-encoded respiratory genes in animal cells.

NRF-1: a trans-activator of nuclear-encoded respiratory genes in animal cells.

Electron transfer in genetically engineered proteins. The cytochrome c paradigm

7.3 Transcriptional Integration of Mitochondrial Biogenesis

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