scholarly journals Direct ETTIN-auxin interaction controls chromatin state in gynoecium development

2019 ◽  
Author(s):  
André Kuhn ◽  
Sigurd Ramans Harborough ◽  
Heather M. McLaughlin ◽  
Stefan Kepinski ◽  
Lars Østergaard
Keyword(s):  
Gene Expression ◽  
Plant Hormone ◽  
Target Genes ◽  
Dependent Manner ◽  
Transcriptional Repressors ◽  
Hormone Interactions ◽  
Related Family ◽  
Repressor Proteins ◽  
Hormone Signalling ◽  
Hormonal Signalling

AbstractHormonal signalling in animals often involves direct transcription factor-hormone interactions that modulate gene expression1, 2. In contrast, plant hormone signalling is most commonly based on de-repression via the degradation of transcriptional repressors3. Recently, we uncovered a non-canonical signalling mechanism for the plant hormone auxin in organ development with strong similarity to animal hormonal pathways. In this mechanism, auxin directly affects the activity of the auxin response factor ETTIN (ETT) towards regulation of target genes without the requirement for protein degradation4, 5. Here we show that auxin binds ETT to modulate gene expression and that this ETT-auxin interaction leads to the dissociation of ETT from co-repressor proteins of the TOPLESS/TOPLESS-RELATED family followed by histone acetylation and the induction of target gene expression. Whilst canonical ARFs are classified as activators or repressors6, ETT is able to switch chromatin locally between repressive and de-repressive states in an instantly-reversible auxin-dependent manner.

scholarly journals Direct ETTIN-auxin interaction controls chromatin states in gynoecium development

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
André Kuhn ◽  
Sigurd Ramans Harborough ◽  
Heather M McLaughlin ◽  
Bhavani Natarajan ◽  
Inge Verstraeten ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plant Hormone ◽  
Target Genes ◽  
Transcriptional Repressors ◽  
Chromatin States ◽  
Hormone Interactions ◽  
Related Family ◽  
Repressor Proteins ◽  
Hormone Signalling ◽  
Hormonal Signalling

Hormonal signalling in animals often involves direct transcription factor-hormone interactions that modulate gene expression. In contrast, plant hormone signalling is most commonly based on de-repression via the degradation of transcriptional repressors. Recently, we uncovered a non-canonical signalling mechanism for the plant hormone auxin whereby auxin directly affects the activity of the atypical auxin response factor (ARF), ETTIN towards target genes without the requirement for protein degradation. Here we show that ETTIN directly binds auxin, leading to dissociation from co-repressor proteins of the TOPLESS/TOPLESS-RELATED family followed by histone acetylation and induction of gene expression. This mechanism is reminiscent of animal hormone signalling as it affects the activity towards regulation of target genes and provides the first example of a DNA-bound hormone receptor in plants. Whilst auxin affects canonical ARFs indirectly by facilitating degradation of Aux/IAA repressors, direct ETTIN-auxin interactions allow switching between repressive and de-repressive chromatin states in an instantly-reversible manner.

scholarly journals Maximal STAT5-Induced Proliferation and Self-Renewal at Intermediate STAT5 Activity Levels

2008 ◽  
Vol 28 (21) ◽  
pp. 6668-6680 ◽  
Author(s):  
Albertus T. J. Wierenga ◽  
Edo Vellenga ◽  
Jan Jacob Schuringa
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Target Genes ◽  
Expression Patterns ◽  
Activity Levels ◽  
Dependent Manner ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions

ABSTRACT The level of transcription factor activity critically regulates cell fate decisions, such as hematopoietic stem cell (HSC) self-renewal and differentiation. We introduced STAT5A transcriptional activity into human HSCs/progenitor cells in a dose-dependent manner by overexpression of a tamoxifen-inducible STAT5A(1*6)-estrogen receptor fusion protein. Induction of STAT5A activity in CD34+ cells resulted in impaired myelopoiesis and induction of erythropoiesis, which was most pronounced at the highest STAT5A transactivation levels. In contrast, intermediate STAT5A activity levels resulted in the most pronounced proliferative advantage of CD34+ cells. This coincided with increased cobblestone area-forming cell and long-term-culture-initiating cell frequencies, which were predominantly elevated at intermediate STAT5A activity levels but not at high STAT5A levels. Self-renewal of progenitors was addressed by serial replating of CFU, and only progenitors containing intermediate STAT5A activity levels contained self-renewal capacity. By extensive gene expression profiling we could identify gene expression patterns of STAT5 target genes that predominantly associated with a self-renewal and long-term expansion phenotype versus those that identified a predominant differentiation phenotype.

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

2010 ◽  
Vol 9 (4) ◽  
pp. 514-531 ◽  
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.

scholarly journals Chromosome 1q amplification perturbs a ceRNA network to promote melanoma metastasis

2021 ◽  
Author(s):  
Xiaonan Xu ◽  
Kaizhen Wang ◽  
Olga Vera ◽  
Akanksha Verma ◽  
Olivier Elemento ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Target Genes ◽  
Melanoma Metastasis ◽  
Dependent Manner ◽  
Suppressor Activity ◽  
Protein Coding ◽  
Chromosome 1Q ◽  
Cerna Network ◽  
Melanoma Progression

Deregulated gene expression through epigenetic, transcriptional, and copy number alterations is a major driver of melanoma progression and metastasis. In addition to serving as blueprints for translation, some mRNAs post-transcriptionally regulate gene expression by competitively sequestering miRNAs they share with other targets. Here we report that such mRNAs, termed competitive endogenous RNAs (ceRNAs), contribute to melanoma progression and metastasis. ceRNA predictions identified multiple candidate genes on chromosome 1q, which is recurrently amplified in melanoma. Genetic studies reveal that three of these mRNAs, CEP170, NUCKS1, and ZC3H11A, promote melanoma migration, invasion, and metastasis in a protein coding-independent and miRNA binding site-dependent manner. Interestingly, CEP170, NUCKS1, and ZC3H11A cooperate to elicit oncogenic effects by collectively impairing the tumor suppressor activity of 8 miRNAs on several pro-metastatic target genes. Finally, this complex chromosome 1q ceRNA network is evident in other cancer types, suggesting ceRNA network deregulation is a common driver of cancer progression.

scholarly journals TREE1-EIN3–mediated transcriptional repression inhibits shoot growth in response to ethylene

2020 ◽  
Vol 117 (46) ◽  
pp. 29178-29189
Author(s):  
Likai Wang ◽  
Eun Esther Ko ◽  
Jaclyn Tran ◽  
Hong Qiao
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Shoot Growth ◽  
Plant Hormone ◽  
Transcriptional Repressor ◽  
Binding Motif ◽  
Dependent Manner ◽  
Ethylene Response ◽  
Dna Motif

Ethylene is an important plant hormone that regulates plant growth, in which the master transcriptionactivator EIN3 (Ethylene Insensitive 3)-mediated transcriptional activation plays vital roles. However, the EIN3-mediated transcriptional repression in ethylene response is unknown. We report here that a Transcriptional Repressor of EIN3-dependent Ethylene-response 1 (TREE1) interacts with EIN3 to regulate transcriptional repression that leads to an inhibition of shoot growth in response to ethylene. Tissue-specific transcriptome analysis showed that most of the genes are down-regulated by ethylene in shoots, and a DNA binding motif was identified that is important for this transcriptional repression. TREE1 binds to the DNA motif to repress gene expression in an EIN3-dependent manner. Genetic validation demonstrated that repression of TREE1-targeted genes leads to an inhibition of shoot growth. Overall, this work establishes a mechanism by which transcriptional repressor TREE1 interacts with EIN3 to inhibit shoot growth via transcriptional repression in response to ethylene.

Huckebein repressor activity in Drosophila terminal patterning is mediated by Groucho

Development ◽  
1999 ◽  
Vol 126 (17) ◽  
pp. 3747-3755 ◽  
Author(s):  
R.E. Goldstein ◽  
G. Jimenez ◽  
O. Cook ◽  
D. Gur ◽  
Z. Paroush
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Target Genes ◽  
Developmental Process ◽  
Dna Binding Proteins ◽  
Gap Gene ◽  
Repressor Proteins ◽  
Developmental Contexts ◽  
Repressor Activity

The Groucho corepressor mediates negative transcriptional regulation in association with various DNA-binding proteins in diverse developmental contexts. We have previously implicated Groucho in Drosophila embryonic terminal patterning, showing that it is required to confine tailless and huckebein terminal gap gene expression to the pole regions of the embryo. Here we reveal an additional requirement for Groucho in this developmental process by establishing that Groucho mediates repressor activity of the Huckebein protein. Putative Huckebein target genes are derepressed in embryos lacking maternal groucho activity and biochemical experiments demonstrate that Huckebein physically interacts with Groucho. Using an in vivo repression assay, we identify a functional repressor domain in Huckebein that contains an FRPW tetrapeptide, similar to the WRPW Groucho-recruitment domain found in Hairy-related repressor proteins. Mutations in Huckebein's FRPW motif abolish Groucho binding and in vivo repression activity, indicating that binding of Groucho through the FRPW motif is required for the repressor function of Huckebein. Taken together with our earlier results, these findings show that Groucho-repression regulates sequential aspects of terminal patterning in Drosophila.

scholarly journals VDR/RXR and TCF4/β-Catenin Cistromes in Colonic Cells of Colorectal Tumor Origin: Impact on c-FOS and c-MYC Gene Expression

2012 ◽  
Vol 26 (1) ◽  
pp. 37-51 ◽  
Author(s):  
Mark B. Meyer ◽  
Paul D. Goetsch ◽  
J. Wesley Pike
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Target Genes ◽  
Direct Action ◽  
Transcriptional Start Site ◽  
Dependent Manner ◽  
Distal Enhancer ◽  
Dihydroxyvitamin D3 ◽  
Regulatory Complex ◽  
Myc Gene

Abstract Many of the transcriptional and growth regulating activities of 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in the intestine and colon are recapitulated in the human colorectal cancer cell LS180. We therefore used this line together with chromatin immunoprecipitation-seq and gene expression analyses to identify the vitamin D receptor (VDR)/retinoid X receptor (RXR) and transcription factor 7-like 2 (TCF7L2/TCF4)/β-catenin cistromes and the genes that they regulate. VDR and RXR colocalized to predominantly promoter distal, vitamin D response element-containing sites in a largely ligand-dependent manner. These regulatory sites control the expression of both known as well as novel 1,25-(OH)2D3 target genes. TCF4 and β-catenin cistromes partially overlapped, contained TCF/lymphoid enhancer-binding factor consensus elements, and were only modestly influenced by 1,25-(OH)2D3. However, the two heterodimer complexes colocalized at sites near a limited set of genes that included c-FOS and c-MYC; the expression of both genes was modulated by 1,25-(OH)2D3. At the c-FOS gene, both VDR/RXR and TCF4/β-catenin bound to a single distal enhancer located 24 kb upstream of the transcriptional start site. At the c-MYC locus, however, binding was noted at a cluster of sites between −139 and −165 kb and at a site located −335 kb upstream. Examined as isolated enhancer fragments, these regions exhibited basal and 1,25-(OH)2D3-inducible activities that were interlinked to both VDR and β-catenin activation. These data reveal additional complexity in the regulation of target genes by 1,25-(OH)2D3 and support a direct action of both VDR and the TCF4/β-catenin regulatory complex at c-FOS and c-MYC.

scholarly journals SAT-441 Transcriptome Analysis Under Differential Thyroid Hormone Treatment During Mouse Cerebellar Development

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Hiroyuki Yajima ◽  
Ishii Sumiyasu ◽  
Wataru Miyazaki ◽  
Noriyuki Koibuchi
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Thyroid Hormone ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Hormone Treatment ◽  
Cerebellar Development ◽  
Mrna Levels ◽  
Dependent Manner

Abstract Background: Thyroid hormone (TH) plays essential roles in the development of the cerebellum by regulating transcription of target genes. TH binds to TH receptor (TR) located in the cell nucleus and stimulates transcription through TH response element (TRE). The expression of many genes is temporary and spatially regulated by TH during cerebellar development. However, the mode of transcription by TR may vary among target genes. In the liver, different duration of TH exposure resulted in distinct gene expression profiles. To examine the mechanisms of transcriptional regulation by TH in cerebellar development, gene expression profile induced by various TH exposure duration was studied. Methods: Anti-thyroid drug propylthiouracil (250 ppm in drinking water) was administered to C57BL/6J mice from the gestational day 14 to postnatal day (P) 7 to generate perinatal hypothyroid mice. To study the effect of continuous TH exposure, TH was subcutaneously administered to hypothyroid pups from P2 to P7 (6 days group). To study the effect of single TH administration, TH was injected on P7 and mice were sacrificed either 6 (6 hours group) or 24 hours (24 hours group) after injection. Cerebellar samples were collected to extract RNA and subject to microarray analysis. Microarray results were confirmed by RT-qPCR. Results: In microarray result, compared with mRNA levels of hypothyroid mice, 6 days group induced upregulation in 1007 genes and downregulation in 1009 genes, 6 hours group induced upregulation in 355 genes and downregulation in 977 genes, and 24 hours group induced upregulation in 365 genes and downregulation in 1121 genes. Only 7.6% of the genes were overlapped in three groups among positively regulated genes. In contrast, 57.2% of the genes were common in the negatively regulated genes. In RT-qPCR result, among genes known to harbor TRE, Hairless, Pcp2, and Nrgn, showed differential upregulation patterns. Hairless was upregulated in all groups, whereas Pcp2 was upregulated only in 5 days group and Nrgn was not upregulated in all groups. These results suggest that different mode of transcriptional regulation occurred in an exposure time-dependent manner of TH. Conclusion: We identified gene groups whose expression were modified by TH during cerebellar development. TH distinctively regulates transcription of target genes depending on the exposure schedule in mouse developing cerebellum.

scholarly journals Protein Arginine Methyltransferase 5 (Prmt5) Promotes Gene Expression of Peroxisome Proliferator-Activated Receptor γ2 (PPARγ2) and Its Target Genes during Adipogenesis

2012 ◽  
Vol 26 (4) ◽  
pp. 583-597 ◽  
Author(s):  
Scott E. LeBlanc ◽  
Silvana Konda ◽  
Qiong Wu ◽  
Yu-Jie Hu ◽  
Christine M. Oslowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Adipogenic Differentiation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adipogenic Gene ◽  
Protein Arginine Methyltransferase 5

Abstract Regulation of adipose tissue formation by adipogenic-regulatory proteins has long been a topic of interest given the ever-increasing health concerns of obesity and type 2 diabetes in the general population. Differentiation of precursor cells into adipocytes involves a complex network of cofactors that facilitate the functions of transcriptional regulators from the CCATT/enhancer binding protein, and the peroxisome proliferator-activated receptor (PPAR) families. Many of these cofactors are enzymes that modulate the structure of chromatin by altering histone-DNA contacts in an ATP-dependent manner or by posttranslationally modifying the histone proteins. Here we report that inhibition of protein arginine methyltransferase 5 (Prmt5) expression in multiple cell culture models for adipogenesis prevented the activation of adipogenic genes. In contrast, overexpression of Prmt5 enhanced adipogenic gene expression and differentiation. Chromatin immunoprecipitation experiments indicated that Prmt5 binds to and dimethylates histones at adipogenic promoters. Furthermore, the presence of Prmt5 promoted the binding of ATP-dependent chromatin-remodeling enzymes and was required for the binding of PPARγ2 at PPARγ2-regulated promoters. The data indicate that Prmt5 acts as a coactivator for the activation of adipogenic gene expression and promotes adipogenic differentiation.

scholarly journals MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity

2020 ◽  
Author(s):  
Ya-Lin Lu ◽  
Yangjian Liu ◽  
Matthew J. McCoy ◽  
Andrew S. Yoo
Keyword(s):  
Gene Expression ◽  
Mirna Target ◽  
Target Gene ◽  
Target Genes ◽  
Dependent Manner ◽  
Neuronal Function ◽  
Mirna Target Gene ◽  
Target Gene Expression ◽  
Human Neurons

SummaryNeuron-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), direct cell fate switching of human fibroblasts to neurons when ectopically expressed by repressing anti-neurogenic genes. How these miRNAs function after the onset of the transcriptome switch to a neuronal fate remains unclear. Here, we identified direct targets of miRNAs by Argonaute (AGO) HITS-CLIP as reprogramming cells activate the neuronal program and reveal the role of miR-124 that directly promotes the expression of its target genes associated with neuronal development and function. The mode of miR-124 as a positive regulator is determined by a neuron-enriched RNA-binding protein, ELAVL3, that interacts with AGO and binds target transcripts, whereas the non-neuronal ELAVL1 counterpart fails to elevate the miRNA-target gene expression. Although existing literature indicate that miRNA-ELAVL1 interaction can result in either target gene upregulation or downregulation in a context-dependent manner, we specifically identified neuronal ELAVL3 as the driver for miRNA target gene upregulation in neurons. In primary human neurons, repressing miR-124 and ELAVL3 led to the downregulation of genes involved in neuronal function and process outgrowth, and cellular phenotypes of reduced inward currents and neurite outgrowth. Results from our study support the role of miR-124 promoting neuronal function through positive regulation of its target genes.

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