The transcription factor Xrp1 is required for PERK-mediated antioxidant gene induction in Drosophila

PERK is an endoplasmic reticulum (ER) transmembrane sensor that phosphorylates eIF2α to initiate the Unfolded Protein Response (UPR). eIF2α phosphorylation promotes stress-responsive gene expression most notably through the transcription factor ATF4 that contains a regulatory 5’ leader. Possible PERK effectors other than ATF4 remain poorly understood. Here, we report that the bZIP transcription factor Xrp1 is required for ATF4-independent PERK signaling. Cell-type-specific gene expression profiling in Drosophila indicated that delta-family glutathione-S-transferases (gstD) are prominently induced by the UPR-activating transgene Rh1G69D. Perk was necessary and sufficient for such gstD induction, but ATF4 was not required. Instead, Perk and other regulators of eIF2α phosphorylation regulated Xrp1 protein levels to induce gstDs. The Xrp1 5’ leader has a conserved upstream Open Reading Frame (uORF) analogous to those that regulate ATF4 translation. The gstD-GFP reporter induction required putative Xrp1 binding sites. These results indicate that antioxidant genes are highly induced by a previously unrecognized UPR signaling axis consisting of PERK and Xrp1.

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The Transcription Factor Xrp1 is Required for PERK-Mediated Antioxidant Gene Induction in Drosophila

10.1101/2021.09.20.461097 ◽

2021 ◽

Author(s):

Brian Brown ◽

Sahana Mitra ◽

Finnegan D Roach ◽

Deepika Vasudevan ◽

Hyung Don Ryoo

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Upstream Open Reading Frame ◽

Bzip Transcription Factor ◽

Specific Gene ◽

Antioxidant Genes ◽

Reading Frame ◽

Protein Levels ◽

Signaling Axis ◽

The Unfolded Protein Response

PERK is an endoplasmic reticulum (ER) transmembrane sensor that phosphorylates eIF2a to initiate the Unfolded Protein Response (UPR). eIF2a phosphorylation promotes stress-responsive gene expression most notably through the transcription factor ATF4 that contains a regulatory 5′ leader. Possible PERK effectors other than ATF4 remain poorly understood. Here, we report that the bZIP transcription factor Xrp1 is required for ATF4-independent PERK signaling. Cell type-specific gene expression profiling in Drosophila indicated that delta-family glutathione-S-transferases (gstD) are prominently induced by the UPR-activating transgene Rh1G69D. Perk was necessary and sufficient for such gstD induction, but ATF4 was not required. Instead, Perk and other regulators of eIF2a phosphorylation regulated Xrp1 protein levels to induce gstDs. The Xrp1 5′ leader has a conserved upstream Open Reading Frame (uORF) analogous to those that regulate ATF4 translation. The gstD-GFP reporter induction required putative Xrp1 binding sites. These results indicate that antioxidant genes are highly induced by a previously unrecognized UPR signaling axis consisting of PERK and Xrp1.

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Sucrose-induced translational repression of plant bZIP-type transcription factors

Biochemical Society Transactions ◽

10.1042/bst0330272 ◽

2005 ◽

Vol 33 (1) ◽

pp. 272-275 ◽

Cited By ~ 35

Author(s):

A. Wiese ◽

N. Elzinga ◽

B. Wobbes ◽

S. Smeekens

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Translational Control ◽

Leucine Zipper ◽

Upstream Open Reading Frame ◽

Bzip Transcription Factor ◽

Reading Frame ◽

Signalling Molecules ◽

Transcription Factor Genes ◽

Plant Genes

Sugars as signalling molecules exert control on the transcription of many plant genes. Sugar signals also alter mRNA and protein stability. Increased sucrose concentrations specifically repress translation of the S-class basic region leucine zipper (bZIP) type transcription factor AtbZIP11/ATB2. This sucrose-induced repression of translation (SIRT) depends on translation of a highly conserved upstream open reading frame (uORF) in the 5′ UTR of the gene. This conserved uORF is exclusively encoded in 5′ UTRs of several plant S-class bZIP transcription factors. Arabidopsis homologues of ATB2/AtbZIP11, which harbour the conserved uORF, also show SIRT. Therefore, SIRT emerges as a general sucrose translational control mechanism of a group of transcription factors. SIRT might be part of a sucrose-specific signalling pathway, controlling expression of plant bZIP transcription factor genes.

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The Dictyostelium bZIP transcription factor DimB regulates prestalk-specific gene expression

Development ◽

10.1242/dev.02190 ◽

2006 ◽

Vol 133 (3) ◽

pp. 439-448 ◽

Cited By ~ 35

Author(s):

N. V. Zhukovskaya

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Bzip Transcription Factor ◽

Specific Gene ◽

Specific Gene Expression

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Genome-wide identification, structural and gene expression analysis of the bZIP transcription factor family in sweet potato wild relative Ipomoea trifida

BMC Genetics ◽

10.1186/s12863-019-0743-y ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 13

Author(s):

Zhengmei Yang ◽

Jian Sun ◽

Yao Chen ◽

Panpan Zhu ◽

Lei Zhang ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Sweet Potato ◽

Gene Expression Analysis ◽

Bzip Transcription Factor ◽

Wild Relative ◽

Transcription Factor Family ◽

Ipomoea Trifida ◽

Genome Wide ◽

Bzip Transcription Factor Family

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FOXA1 in breast cancer

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399409001008 ◽

2009 ◽

Vol 11 ◽

Cited By ~ 39

Author(s):

Harikrishna Nakshatri ◽

Sunil Badve

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Transcription Factor ◽

Expression Patterns ◽

Gene Expression Pattern ◽

Gene Expression Signature ◽

Specific Gene ◽

Breast Cancers ◽

Transcription Factor Network ◽

Histopathological Classification

Breast cancer is a heterogeneous disease and classification is important for clinical management. At least five subtypes can be identified based on unique gene expression patterns; this subtype classification is distinct from the histopathological classification. The transcription factor network(s) required for the specific gene expression signature in each of these subtypes is currently being elucidated. The transcription factor network composed of the oestrogen (estrogen) receptor α (ERα), FOXA1 and GATA3 may control the gene expression pattern in luminal subtype A breast cancers. Breast cancers that are dependent on this network correspond to well-differentiated and hormone-therapy-responsive tumours with good prognosis. In this review, we discuss the interplay between these transcription factors with a particular emphasis on FOXA1 structure and function, and its ability to control ERα function. Additionally, we discuss modulators of FOXA1 function, ERα–FOXA1–GATA3 downstream targets, and potential therapeutic agents that may increase differentiation through FOXA1.

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Disappearance of the sigma E transcription factor from the forespore and the SpoIIE phosphatase from the mother cell contributes to establishment of cell-specific gene expression during sporulation in Bacillus subtilis.

Journal of Bacteriology ◽

10.1128/jb.179.10.3331-3341.1997 ◽

1997 ◽

Vol 179 (10) ◽

pp. 3331-3341 ◽

Cited By ~ 77

Author(s):

K Pogliano ◽

A E Hofmeister ◽

R Losick

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Bacillus Subtilis ◽

Mother Cell ◽

Specific Gene ◽

Specific Gene Expression ◽

Sigma E

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The TEA Transcription Factor Tec1 Confers Promoter-Specific Gene Regulation by Ste12-Dependent and -Independent Mechanisms

Eukaryotic Cell ◽

10.1128/ec.00251-09 ◽

2010 ◽

Vol 9 (4) ◽

pp. 514-531 ◽

Cited By ~ 20

Author(s):

Barbara Heise ◽

Julia van der Felden ◽

Sandra Kern ◽

Mario Malcher ◽

Stefan Brückner ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcriptional Activation ◽

Binding Sites ◽

Target Genes ◽

Specific Gene ◽

Dependent Manner ◽

A Genome ◽

Regulated Gene Expression

ABSTRACT In Saccharomyces cerevisiae, the TEA transcription factor Tec1 is known to regulate target genes together with a second transcription factor, Ste12. Tec1-Ste12 complexes can activate transcription through Tec1 binding sites (TCSs), which can be further combined with Ste12 binding sites (PREs) for cooperative DNA binding. However, previous studies have hinted that Tec1 might regulate transcription also without Ste12. Here, we show that in vivo, physiological amounts of Tec1 are sufficient to stimulate TCS-mediated gene expression and transcription of the FLO11 gene in the absence of Ste12. In vitro, Tec1 is able to bind TCS elements with high affinity and specificity without Ste12. Furthermore, Tec1 contains a C-terminal transcriptional activation domain that confers Ste12-independent activation of TCS-regulated gene expression. On a genome-wide scale, we identified 302 Tec1 target genes that constitute two distinct classes. A first class of 254 genes is regulated by Tec1 in a Ste12-dependent manner and is enriched for genes that are bound by Tec1 and Ste12 in vivo. In contrast, a second class of 48 genes can be regulated by Tec1 independently of Ste12 and is enriched for genes that are bound by the stress transcription factors Yap6, Nrg1, Cin5, Skn7, Hsf1, and Msn4. Finally, we find that combinatorial control by Tec1-Ste12 complexes stabilizes Tec1 against degradation. Our study suggests that Tec1 is able to regulate TCS-mediated gene expression by Ste12-dependent and Ste12-independent mechanisms that enable promoter-specific transcriptional control.

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The Repressor Element 1-Silencing Transcription Factor Regulates Heart-Specific Gene Expression Using Multiple Chromatin-Modifying Complexes

Molecular and Cellular Biology ◽

10.1128/mcb.00269-07 ◽

2007 ◽

Vol 27 (11) ◽

pp. 4082-4092 ◽

Cited By ~ 40

Author(s):

Andrew J. Bingham ◽

Lezanne Ooi ◽

Lukasz Kozera ◽

Edward White ◽

Ian C. Wood

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Cardiac Hypertrophy ◽

Gene Expression Profile ◽

Expression Profile ◽

Molecular Mechanisms ◽

Ventricular Myocytes ◽

Specific Gene ◽

Histone H4 Acetylation ◽

Repressor Element

ABSTRACT Cardiac hypertrophy is associated with a dramatic change in the gene expression profile of cardiac myocytes. Many genes important during development of the fetal heart but repressed in the adult tissue are reexpressed, resulting in gross physiological changes that lead to arrhythmias, cardiac failure, and sudden death. One transcription factor thought to be important in repressing the expression of fetal genes in the adult heart is the transcriptional repressor REST (repressor element 1-silencing transcription factor). Although REST has been shown to repress several fetal cardiac genes and inhibition of REST function is sufficient to induce cardiac hypertrophy, the molecular mechanisms employed in this repression are not known. Here we show that continued REST expression prevents increases in the levels of the BNP (Nppb) and ANP (Nppa) genes, encoding brain and atrial natriuretic peptides, in adult rat ventricular myocytes in response to endothelin-1 and that inhibition of REST results in increased expression of these genes in H9c2 cells. Increased expression of Nppb and Nppa correlates with increased histone H4 acetylation and histone H3 lysine 4 methylation of promoter-proximal regions of these genes. Furthermore, using deletions of individual REST repression domains, we show that the combined activities of two domains of REST are required to efficiently repress transcription of the Nppb gene; however, a single repression domain is sufficient to repress the Nppa gene. These data provide some of the first insights into the molecular mechanism that may be important for the changes in gene expression profile seen in cardiac hypertrophy.

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