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 Novel Mechanism of Positive versus Negative Regulation by Thyroid Hormone Receptor β1 (TRβ1) Identified by Genome-wide Profiling of Binding Sites in Mouse Liver

2013 ◽  
Vol 289 (3) ◽  
pp. 1313-1328 ◽  
Author(s):  
Preeti Ramadoss ◽  
Brian J. Abraham ◽  
Linus Tsai ◽  
Yiming Zhou ◽  
Ricardo H. Costa-e-Sousa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Thyroid Hormone ◽  
Binding Sites ◽  
Hormone Receptor ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Negative Regulation ◽  
Genome Wide

Triiodothyronine (T3) regulates key metabolic processes in the liver through the thyroid hormone receptor, TRβ1. However, the number of known target genes directly regulated by TRβ1 is limited, and the mechanisms by which positive and especially negative transcriptional regulation occur are not well understood. To characterize the TRβ1 cistrome in vivo, we expressed a biotinylated TRβ1 in hypo- and hyperthyroid mouse livers, used ChIP-seq to identify genomic TRβ1 targets, and correlated these data with gene expression changes. As with other nuclear receptors, the majority of TRβ1 binding sites were not in proximal promoters but in the gene body of known genes. Remarkably, T3 can dictate changes in TRβ1 binding, with strong correlation to T3-induced gene expression changes, suggesting that differential TRβ1 binding regulates transcriptional outcome. Additionally, DR-4 and DR-0 motifs were significantly enriched at binding sites where T3 induced an increase or decrease in TRβ1 binding, respectively, leading to either positive or negative regulation by T3. Taken together, the results of this study provide new insights into the mechanisms of transcriptional regulation by TRβ1 in vivo.

Targeting gene expression to the head: the Drosophila orthodenticle gene is a direct target of the Bicoid morphogen

Development ◽  
1998 ◽  
Vol 125 (21) ◽  
pp. 4185-4193 ◽  
Author(s):  
Q. Gao ◽  
R. Finkelstein
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Regulatory Element ◽  
Regulatory Region ◽  
Repeated Sequence ◽  
Drosophila Embryo ◽  
Sequence Motif ◽  
Specific Expression ◽  
Gap Gene

The Bicoid (Bcd) morphogen establishes the head and thorax of the Drosophila embryo. Bcd activates the transcription of identified target genes in the thoracic segments, but its mechanism of action in the head remains poorly understood. It has been proposed that Bcd directly activates the cephalic gap genes, which are the first zygotic genes to be expressed in the head primordium. It has also been suggested that the affinity of Bcd-binding sites in the promoters of Bcd target genes determines the posterior extent of their expression (the Gene X model). However, both these hypotheses remain untested. Here, we show that a small regulatory region upstream of the cephalic gap gene orthodenticle (otd) is sufficient to recapitulate early otd expression in the head primordium. This region contains two control elements, each capable of driving otd-like expression. The first element has consensus Bcd target sites that bind Bcd in vitro and are necessary for head-specific expression. As predicted by the Gene X model, this element has a relatively low affinity for Bcd. Surprisingly, the second regulatory element has no Bcd sites. Instead, it contains a repeated sequence motif similar to a regulatory element found in the promoters of otd-related genes in vertebrates. Our study is the first demonstration that a cephalic gap gene is directly regulated by Bcd. However, it also shows that zygotic gene expression can be targeted to the head primordium without direct Bcd regulation.

scholarly journals Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the unfolded protein response (UPR) in models of neurodegeneration

2020 ◽  
Author(s):  
René L. Vidal ◽  
Denisse Sepulveda ◽  
Paulina Troncoso-Escudero ◽  
Paula Garcia-Huerta ◽  
Constanza Gonzalez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Unfolded Protein Response ◽  
Target Genes ◽  
Cell Function ◽  
Alpha Synuclein ◽  
Protective Effects ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractAlteration to endoplasmic reticulum (ER) proteostasis is observed on a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteostasis and cell function. The UPR is initiated by specialized stress sensors that engage gene expression programs through the concerted action of the transcription factors ATF4, ATF6f, and XBP1s. Although UPR signaling is generally studied as unique linear signaling branches, correlative evidence suggests that ATF6f and XBP1s may physically interact to regulate a subset of UPR-target genes. Here, we designed an ATF6f-XBP1s fusion protein termed UPRplus that behaves as a heterodimer in terms of its selective transcriptional activity. Cell-based studies demonstrated that UPRplus has stronger an effect in reducing the abnormal aggregation of mutant huntingtin and alpha-synuclein when compared to XBP1s or ATF6 alone. We developed a gene transfer approach to deliver UPRplus into the brain using adeno-associated viruses (AAVs) and demonstrated potent neuroprotection in vivo in preclinical models of Parkinson’s and Huntington’s disease. These results support the concept where directing UPR-mediated gene expression toward specific adaptive programs may serve as a possible strategy to optimize the beneficial effects of the pathway in different disease conditions.

scholarly journals Effect of destrin mutations on the gene expression profile in vivo

2008 ◽  
Vol 34 (1) ◽  
pp. 9-21 ◽  
Author(s):  
Angela M. Verdoni ◽  
Natsuyo Aoyama ◽  
Akihiro Ikeda ◽  
Sakae Ikeda
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Target Genes ◽  
Actin Dynamics ◽  
In Vivo Model ◽  
Strong Impact ◽  
Filamentous Actin ◽  
Control Of Gene Expression

Remodeling of the actin cytoskeleton through actin dynamics (assembly and disassembly of filamentous actin) is known to be essential for numerous basic biological processes. In addition, recent studies have provided evidence that actin dynamics participate in the control of gene expression. A spontaneous mouse mutant, corneal disease 1 ( corn1), is deficient for a regulator of actin dynamics, destrin (DSTN, also known as ADF), which causes epithelial hyperproliferation and neovascularization in the cornea. Dstn corn1 mice exhibit an actin dynamics defect in the corneal epithelial cells, offering an in vivo model to investigate cellular mechanisms affected by the Dstn mutation and resultant actin dynamics abnormalities. To examine the effect of the Dstn corn1 mutation on the gene expression profile, we performed a microarray analysis using the cornea from Dstn corn1 and wild-type mice. A dramatic alteration of the gene expression profile was observed in the Dstn corn1 cornea, with 1,226 annotated genes differentially expressed. Functional annotation of these genes revealed that the most significantly enriched functional categories are associated with actin and/or cytoskeleton. Among genes that belong to these categories, a considerable number of serum response factor target genes were found, indicating the possible existence of an actin-SRF pathway of transcriptional regulation in vivo. A comparative study using an allelic mutant strain with milder corneal phenotypes suggested that the level of filamentous actin may correlate with the level of gene expression changes. Our study shows that Dstn mutations and resultant actin dynamics abnormalities have a strong impact on the gene expression profile in vivo.

scholarly journals In vivo transcriptional regulation of N-Myc target genes is controlled by E-box methylation

2005 ◽  
Vol 102 (34) ◽  
pp. 12117-12122 ◽  
Author(s):  
G. Perini ◽  
D. Diolaiti ◽  
A. Porro ◽  
G. Della Valle
Keyword(s):  
Transcriptional Regulation ◽  
Target Genes ◽  
E Box

scholarly journals Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets

2016 ◽  
Vol 113 (13) ◽  
pp. E1835-E1843 ◽  
Author(s):  
Mina Fazlollahi ◽  
Ivor Muroff ◽  
Eunjee Lee ◽  
Helen C. Causton ◽  
Harmen J. Bussemaker
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Nonsynonymous Mutation ◽  
Gene Regulatory ◽  
Genetic Modulators

Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting natural variation is a potent strategy for probing functional interactions within gene regulatory networks. We developed an algorithm to identify genetic polymorphisms that modulate the regulatory connectivity between specific transcription factors and their target genes in vivo. As a proof of principle, we mapped connectivity quantitative trait loci (cQTLs) using parallel genotype and gene expression data for segregants from a cross between two strains of the yeast Saccharomyces cerevisiae. We identified a nonsynonymous mutation in the DIG2 gene as a cQTL for the transcription factor Ste12p and confirmed this prediction empirically. We also identified three polymorphisms in TAF13 as putative modulators of regulation by Gcn4p. Our method has potential for revealing how genetic differences among individuals influence gene regulatory networks in any organism for which gene expression and genotype data are available along with information on binding preferences for transcription factors.

130 A CATALOG OF REFERENCE GENES WITH HIGH, MEDIUM, AND LOW LEVELS OF EXPRESSION DURING BOVINE IN VIVO PRE-IMPLANTATION DEVELOPMENT

2017 ◽  
Vol 29 (1) ◽  
pp. 173
Author(s):  
Z. Jiang ◽  
J. Sun ◽  
S. Marjani ◽  
H. Dong ◽  
X. Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reference Genes ◽  
Target Genes ◽  
Stable Expression ◽  
Bovine Embryo ◽  
Rna Seq ◽  
Rt Pcr ◽  
Data Set ◽  
Low Expression

Appropriate reference genes for accurate normalization in RT-PCR are essential for the study of gene expression. Ideal reference genes should not only have stable expression across stages of embryo development, but also be expressed at comparable levels to the target genes. Using RNA-seq data from in vivo-produced bovine oocytes and embryos from the 2-cell to blastocyst stage (Jiang et al., 2014 BMC Genomics 15, 756), we tried to establish a catalogue of all reference genes for RT-PCR analysis. One-way ANOVA generated 4055 genes that did not differ across stages. To reduce this list, we used the entire RNA-seq data set and first removed genes with a FPKM (fragments per kilobase of transcript per million mapped reads) of <1, and then rescaled each gene’s expression values within a range of 0 to 1. We subsequently calculated the expression variance for each gene across all stages. By assuming that the calculated variances follow a Gaussian distribution and that the majority of the genes do not have a stable expression level, a gene was classified as a reference if its variance significantly deviated (P < 0.05) from these assumptions. We identified 346 potential reference genes, all of which were among the candidates from the ANOVA analysis. We arbitrarily assigned genes in this list to high (FPKM ≥ 100), medium (10 < FPKM < 100), and low expression levels (FPKM ≤ 10), and 37, 154, and 155 genes, respectively, fell into these groups. Surprisingly, none of the commonly used reference genes, such as GAPDH, PPIA, ACTB, PRL15, GUSB, and H3F2A, were identified as being stably expressed across in vivo development. This is consistent with findings of prior RT-PCR studies (Robert et al. 2002 Biol. Reprod. 67, 1465–1472; Ross et al. 2010 Cell Reprogram. 12, 709–717). The following gene ontology terms were significantly enriched for the 346 genes: cell cycle, translation, transport, chromatin, cell division, and metabolic process, indicating that the early embryos maintained constant levels of genes involved in fundamental biological functions. Finally, we performed RT-PCR to validate the RNA-seq results using different bovine in vivo-derived oocytes and embryos (n = 3/stage). We successfully validated 10 selected genes, including those in the high (CS, PGD, and ACTR3), medium (CCT5, MRPL47, COG2, CRT9, and HELLS), and low expression groups (CDC23 and TTF1). In conclusion, we recommend the use of reference genes that are expressed at comparable levels to target genes. This study offers a useful resource to aid in the appropriate selection of reference genes, which will improve the accuracy of quantitative gene expression analyses across bovine embryo pre-implantation development.

scholarly journals Analysis of Rice Proteins with DLN Repressor Motif/S

2019 ◽  
Vol 20 (7) ◽  
pp. 1600 ◽  
Author(s):  
Purnima Singh ◽  
Iny Mathew ◽  
Ankit Verma ◽  
Akhilesh Tyagi ◽  
Pinky Agarwal
Keyword(s):  
Transcriptional Regulation ◽  
Oryza Sativa ◽  
Transcription Factors ◽  
Reporter Genes ◽  
Transcriptional Regulators ◽  
Terminal Region ◽  
Relative Percentage ◽  
Repressor Proteins ◽  
Encoding Genes ◽  
Repressor Activity

Transcriptional regulation includes both activation and repression of downstream genes. In plants, a well-established class of repressors are proteins with an ERF-associated amphiphilic repression/EAR domain. They contain either DLNxxP or LxLxL as the identifying hexapeptide motif. In rice (Oryza sativa), we have identified a total of 266 DLN repressor proteins, with the former motif and its modifications thereof comprising 227 transcription factors and 39 transcriptional regulators. Apart from DLNxxP motif conservation, DLNxP and DLNxxxP motifs with variable numbers/positions of proline and those without any proline conservation have been identified. Most of the DLN repressome proteins have a single DLN motif, with higher relative percentage in the C-terminal region. We have designed a simple yeast-based experiment wherein a DLN motif can successfully cause strong repression of downstream reporter genes, when fused to a transcriptional activator of rice or yeast. The DLN hexapeptide motif is essential for repression, and at least two “DLN” residues cause maximal repression. Comparatively, rice has more DLN repressor encoding genes than Arabidopsis, and DLNSPP motif from rice is 40% stronger than the known Arabidopsis SRDX motif. The study reports a straightforward assay to analyze repressor activity, along with the identification of a strong DLN repressor from rice.

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 Epigenetic regulation of neural cell differentiation plasticity in the adult mammalian brain

2008 ◽  
Vol 105 (46) ◽  
pp. 18012-18017 ◽  
Author(s):  
Jun Kohyama ◽  
Takuro Kojima ◽  
Eriko Takatsuka ◽  
Toru Yamashita ◽  
Jun Namiki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Epigenetic Modification ◽  
Mammalian Brain ◽  
Cytokine Signaling ◽  
Specific Gene ◽  
Neural Cells ◽  
Specific Gene Expression

Neural stem/progenitor cells (NSCs/NPCs) give rise to neurons, astrocytes, and oligodendrocytes. It has become apparent that intracellular epigenetic modification including DNA methylation, in concert with extracellular cues such as cytokine signaling, is deeply involved in fate specification of NSCs/NPCs by defining cell-type specific gene expression. However, it is still unclear how differentiated neural cells retain their specific attributes by repressing cellular properties characteristic of other lineages. In previous work we have shown that methyl-CpG binding protein transcriptional repressors (MBDs), which are expressed predominantly in neurons in the central nervous system, inhibit astrocyte-specific gene expression by binding to highly methylated regions of their target genes. Here we report that oligodendrocytes, which do not express MBDs, can transdifferentiate into astrocytes both in vitro (cytokine stimulation) and in vivo (ischemic injury) through the activation of the JAK/STAT signaling pathway. These findings suggest that differentiation plasticity in neural cells is regulated by cell-intrinsic epigenetic mechanisms in collaboration with ambient cell-extrinsic cues.

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