An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli

Hashimoto, Yoshinori; Zhang, Chun; Kawauchi, Junya; Imoto, Issei; Adachi, Mio; Inazawa, Johji; Amagasa, Teruo; Hai, Tsonwin; Kitajima, Shigetaka

doi:10.1093/nar/30.11.2398

Cited by 83 publications

(76 citation statements)

References 37 publications

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“…For example, the isoforms ATF3⌬Zip2a and ATF3⌬Zip2b were isolated from cells treated with stimuli such as calcium ionophore A23187, TNF-␣, endoplasmic reticulum stress, or oxidative stress 36 ; other isoforms, such as ATF3⌬Zip2c or ATF3⌬Zip3, have also been reported. 37 Because some of these splicing variants code for C-terminal deletion proteins and were found to counteract the transcriptional regulation by full-length ATF3 in a reporter assay, 36 additional studies are needed to further clarify whether these alternatively spliced isoforms are indeed expressed and, if so, the functional roles they play under renal I/R conditions.…”

Section: Discussionmentioning

confidence: 99%

ATF3-Mediated Epigenetic Regulation Protects against Acute Kidney Injury

Cheng

Liao

et al. 2010

Journal of the American Society of Nephrology

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A variety of stress stimuli, including ischemia-reperfusion (I/R) injury, induce the transcriptional repressor ATF3 in the kidney. The functional consequences of this upregulation in ATF3 after renal I/R injury are not well understood. Here, we found that ATF3-deficient mice had higher renal I/R-induced mortality, kidney dysfunction, inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin), and apoptosis compared with wild-type mice. Furthermore, gene transfer of ATF3 to the kidney rescued the renal I/R-induced injuries in the ATF3-deficient mice. Molecular and biochemical analysis revealed that ATF3 interacted directly with histone deacetylase 1 (HDAC1) and recruited HDAC1 into the ATF/NF-B sites in the IL-6 and IL-12b gene promoters. The ATF3-associated HDAC1 deacetylated histones, which resulted in the condensation of chromatin structure, interference of NF-B binding, and inhibition of inflammatory gene transcription after I/R injury. Taken together, these data demonstrate epigenetic regulation mediated by the stress-inducible gene ATF3 after renal I/R injury and suggest potential targeted approaches for acute kidney injury.

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Section: Discussionmentioning

confidence: 99%

ATF3-Mediated Epigenetic Regulation Protects against Acute Kidney Injury

Cheng

Liao

et al. 2010

Journal of the American Society of Nephrology

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“…Using an antibody specific for the C-terminal region of ATF3, but not that of ATF3⌬Zip and ATF3⌬Zip2 (17), both ATF3 (upper band) and ATF3b (lower band) were detected in ␣TC1.6 cells, and both were down-regulated by glucose (Fig. 2B).…”

Section: Cloning and Characterization Of A Novel Isoform Ofmentioning

confidence: 99%

“…Two C-terminal truncated isoforms, ATF3⌬Zip and ATF3⌬Zip2, which lack the leucine zipper domain, have been isolated from human tissue. These fail to bind to the ATF/CRE sites (16,17). The corresponding isoforms have not yet been described in rodents.…”

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confidence: 99%

Regulation of Proglucagon Transcription by Activated Transcription Factor (ATF) 3 and a Novel Isoform, ATF3b, through the cAMP-response Element/ATF Site of the Proglucagon Gene Promoter

Wang

Cao

Steiner

2003

Journal of Biological Chemistry

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Glucagon, the second major glucose-regulated hormone in the control of glucose homeostasis, functions as a counter-regulator to insulin and is specifically produced by the pancreatic ␣ cells. Its excessive biosynthesis and secretion is associated with diabetes mellitus. The expression of the proglucagon gene has been demonstrated to be regulated by a cAMP-dependent pathway through cAMP-response element-binding protein (CREB) and possibly other transcription factors bound to its cAMP-response element (CRE)/activated transcription factor (ATF) site. Elsewhere we have shown that ATF3, a member of the ATF/CREB subfamily of the basic leucine zipper domain proteins, is expressed predominantly in the ␣ cells of the pancreatic islets. In our attempts to further dissect the role of ATF3 proteins in ␣ cells, we have identified and characterized a novel alternatively spliced form, ATF3b, and have compared the specific binding ability of ATF3 and ATF3b on the CRE/ ATF motif of the proglucagon promoter. Our findings indicate the existence of a novel mechanism by which the transcription of the proglucagon gene is regulated in response to cAMP signals, in addition to CREB and in relation to glucose fluctuations in pancreatic ␣ cells.

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“…Translation from pre-existing ATF4 mRNA is enhanced in stress conditions that lead to eIF-2␣ phosphorylation, including amino acid deprivation (9), ER stress (10), the presence of long double strand RNA (11), and heme deficiency (12). ATF3 is expressed at low levels in normal and quiescent cells but can be rapidly induced in response to diverse stress signals and is likely to be involved in controlling a wide variety of cellular activities (13,14). As the result of alternative splicing, activated transcription from the ATF3 gene results in several different mRNA species, encoding proteins of different sequence, coding frames, and length (4, 14 -16).…”

mentioning

confidence: 99%

Amino Acid Deprivation Induces the Transcription Rate of the Human Asparagine Synthetase Gene through a Timed Program of Expression and Promoter Binding of Nutrient-responsive Basic Region/Leucine Zipper Transcription Factors as Well as Localized Histone Acetylation

Chen¹,

Pan²,

Dudenhausen

et al. 2004

Journal of Biological Chemistry

177

240

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Expression of human asparagine synthetase (ASNS), which catalyzes asparagine and glutamate biosynthesis, is transcriptionally induced following amino acid deprivation. Previous overexpression and electrophoresis mobility shift analysis showed the involvement of the transcription factors ATF4, C/EBP␤, and ATF3-FL through the nutrient-sensing response element-1 (NSRE-1) within the ASNS promoter. Amino acid deprivation caused an elevated mRNA level for ATF4, C/EBP␤, and ATF3-FL, and the present study established that the nuclear protein content for ATF4 and ATF3-FL were increased during amino acid limitation, whereas C/EBP␤-LIP declined slightly. The total amount of C/EBP␤-LAP protein was unchanged, but changes in the distribution among multiple C/EBP␤-LAP forms were observed. Overexpression studies established that ATF4, ATF3-FL, and C/EBP␤-LAP could coordinately modulate the transcription from the human ASNS promoter. Chromatin immunoprecipitation demonstrated that amino acid deprivation increased ATF3-FL, ATF4, and C/EBP␤ binding to the ASNS promoter and enhanced promoter association of RNA polymerase II, TATA-binding protein, and TFIIB of the general transcription machinery. A time course revealed a markedly different temporal order of interaction between these transcription factors and the ASNS promoter. During the initial 2 h, there was a 20-fold increase in ATF4 binding and a rapid increase in histone H3 and H4 acetylation, which closely paralleled the increased transcription rate of the ASNS gene, whereas the increase in ATF3-FL and C/EBP␤ binding was considerably slower and more closely correlated with the decline in transcription rate between 2 and 6 h. The data suggest that ATF3-FL and C/EBP␤ act as transcriptional suppressors for the ASNS gene to counterbalance the transcription rate activated by ATF4 following amino acid deprivation.

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An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli

Cited by 83 publications

References 37 publications

ATF3-Mediated Epigenetic Regulation Protects against Acute Kidney Injury

ATF3-Mediated Epigenetic Regulation Protects against Acute Kidney Injury

Regulation of Proglucagon Transcription by Activated Transcription Factor (ATF) 3 and a Novel Isoform, ATF3b, through the cAMP-response Element/ATF Site of the Proglucagon Gene Promoter

Amino Acid Deprivation Induces the Transcription Rate of the Human Asparagine Synthetase Gene through a Timed Program of Expression and Promoter Binding of Nutrient-responsive Basic Region/Leucine Zipper Transcription Factors as Well as Localized Histone Acetylation

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