scholarly journals Mutant Alleles of the Drosophila trithorax Gene Produce Common and Unusual Homeotic and Other Developmental Phenotypes

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 319-344
Author(s):  
Thomas R Breen
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Protein Isoforms ◽  
Homeotic Genes ◽  
Set Domain ◽  
Human Homologue ◽  
Terminal Set ◽  
Hypomorphic Alleles ◽  
Different Levels ◽  
Target Gene Transcription

Abstract trithorax (trx) encodes chromosome-binding proteins required throughout embryogenesis and imaginal development for tissue- and cell-specific levels of transcription of many genes including homeotic genes of the ANT-C and BX-C. trx encodes two protein isoforms that contain conserved motifs including a C-terminal SET domain, central PHD fingers, an N-terminal DNA-binding homology, and two short motifs also found in the TRX human homologue, ALL1. As a first step to characterizing specific developmental functions of TRX, I examined phenotypes of 420 combinations of 21 trx alleles. Among these are 8 hypomorphic alleles that are sufficient for embryogenesis but provide different levels of trx function at homeotic genes in imaginal cells. One allele alters the N terminus of TRX, which severely impairs larval and imaginal growth. Hypomorphic alleles that alter different regions of TRX equivalently reduce function at affected genes, suggesting TRX interacts with common factors at different target genes. All hypomorphic alleles examined complement one another, suggesting cooperative TRX function at target genes. Comparative effects of hypomorphic genotypes support previous findings that TRX has tissue-specific interactions with other factors at each target gene. Some hypomorphic genotypes also produce phenotypes that suggest TRX may be a component of signal transduction pathways that provide tissue- and cell-specific levels of target gene transcription.

scholarly journals PPARgene: A Database of Experimentally Verified and Computationally Predicted PPAR Target Genes

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Li Fang ◽  
Man Zhang ◽  
Yanhui Li ◽  
Yan Liu ◽  
Qinghua Cui ◽  
...  
Keyword(s):  
In Silico ◽  
Target Gene ◽  
Target Genes ◽  
Prediction Method ◽  
Peroxisome Proliferator ◽  
Physiological Processes ◽  
Peroxisome Proliferator Activated Receptors ◽  
High Throughput Gene Expression ◽  
Responsive Element ◽  
Target Gene Transcription

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear receptor superfamily. Upon ligand binding, PPARs activate target gene transcription and regulate a variety of important physiological processes such as lipid metabolism, inflammation, and wound healing. Here, we describe the first database of PPAR target genes, PPARgene. Among the 225 experimentally verified PPAR target genes, 83 are for PPARα, 83 are for PPARβ/δ, and 104 are for PPARγ. Detailed information including tissue types, species, and reference PubMed IDs was also provided. In addition, we developed a machine learning method to predict novel PPAR target genes by integratingin silicoPPAR-responsive element (PPRE) analysis with high throughput gene expression data. Fivefold cross validation showed that the performance of this prediction method was significantly improved compared to thein silicoPPRE analysis method. The prediction tool is also implemented in the PPARgene database.

scholarly journals Sp5 and Sp8 recruit β-catenin and Tcf1-Lef1 to select enhancers to activate Wnt target gene transcription

2016 ◽  
Vol 113 (13) ◽  
pp. 3545-3550 ◽  
Author(s):  
Mark W. Kennedy ◽  
Ravindra B. Chalamalasetty ◽  
Sara Thomas ◽  
Robert J. Garriock ◽  
Parthav Jailwala ◽  
...  
Keyword(s):  
Cell Fate ◽  
Target Gene ◽  
Target Genes ◽  
Wnt Signaling Pathway ◽  
Embryonic Stem ◽  
T Cell Factor ◽  
Core Components ◽  
Specificity Protein ◽  
Wnt Signal ◽  
Target Gene Transcription

The ancient, highly conserved, Wnt signaling pathway regulates cell fate in all metazoans. We have previously shown that combined null mutations of the specificity protein (Sp) 1/Klf-like zinc-finger transcription factors Sp5 and Sp8 (i.e., Sp5/8) result in an embryonic phenotype identical to that observed when core components of the Wnt/β-catenin pathway are mutated; however, their role in Wnt signal transduction is unknown. Here, we show in mouse embryos and differentiating embryonic stem cells that Sp5/8 are gene-specific transcriptional coactivators in the Wnt/β-catenin pathway. Sp5/8 bind directly to GC boxes in Wnt target gene enhancers and to adjacent, or distally positioned, chromatin-bound T-cell factor (Tcf) 1/lymphoid enhancer factor (Lef) 1 to facilitate recruitment of β-catenin to target gene enhancers. Because Sp5 is itself directly activated by Wnt signals, we propose that Sp5 is a Wnt/β-catenin pathway-specific transcripton factor that functions in a feed-forward loop to robustly activate select Wnt target genes.

scholarly journals A Functional Interaction between RIP140 and PGC-1α Regulates the Expression of the Lipid Droplet Protein CIDEA

2008 ◽  
Vol 28 (22) ◽  
pp. 6785-6795 ◽  
Author(s):  
Magnus Hallberg ◽  
Daniel L. Morganstein ◽  
Evangelos Kiskinis ◽  
Kunal Shah ◽  
Anastasia Kralli ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Energy Homeostasis ◽  
Target Gene ◽  
Target Genes ◽  
Cell Function ◽  
Functional Interaction ◽  
Brown Adipocytes ◽  
Target Gene Transcription ◽  
Lipid Droplet Protein ◽  
Estrogen Related Receptor

ABSTRACT Nuclear receptors activate or repress target genes depending on the recruitment of coactivators or corepressors. The corepressor RIP140 and the PPAR coactivator 1α (PGC-1α) both play key roles in the regulated transcription of genes involved in energy homeostasis. We investigated the roles of RIP140 and PGC-1α in controlling the expression of CIDEA, an important regulatory factor in adipose cell function and obesity. Ectopically expressed CIDEA surrounded lipid droplets in brown adipocytes and induced the formation of lipid droplets in nonadipogenic cell lines. The expression and promoter activity of CIDEA was repressed by RIP140 and induced by PGC-1α, mediated through the binding of estrogen-related receptor α and NRF-1 to their cognate binding sites. Importantly, we demonstrate that RIP140 interacts directly with PGC-1α and suppresses its activity. The direct antagonism of PGC-1α by RIP140 provides a mechanism for regulating target gene transcription via nuclear receptor-dependent and -independent pathways.

Identification and characterization of a gene activated by the deformed homeoprotein

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 203-214 ◽  
Author(s):  
J.W. Mahaffey ◽  
D.F. Jones ◽  
J.A. Hickel ◽  
C.M. Griswold
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Direct Interaction ◽  
Homeotic Genes ◽  
Binding Assays ◽  
Transcript Accumulation ◽  
Enhancer Element ◽  
Control Segment ◽  
The Individual

In Drosophila, the homeotic genes encode transcription factors which control segment identity during embryogenesis by specifying the appropriate set of ‘target’ genes necessary to produce the individual segmental characteristics. Though we know much about the homeotic genes and the proteins they encode, we know little of their targets. Here we identify and characterize one such target gene, a gene activated by the product of the homeotic gene Deformed. DNA binding assays and expression of reporter gene constructs indicate that activation of this gene requires a direct interaction between the Deformed protein and an upstream enhancer element at this target gene. However, although Deformed is required to activate this gene in cells of the maxillary segment, ectopically expressed Deformed does not activate the gene in other regions of the embryo. We conclude from this and other observations that additional factors may be required to activate the target gene, and, therefore, Deformed may participate in either a combinatorial or hierarchical activation signal in the maxillary cells. This newly identified gene encodes a novel protein of unknown function, though proteins with similar amino acid composition have been found. The pattern of transcript accumulation during embryogenesis indicates that this gene may be regulated by other homeoproteins in addition to Deformed.

scholarly journals Crucial Roles for Interactions between MLL3/4 and INI1 in Nuclear Receptor Transactivation

2009 ◽  
Vol 23 (5) ◽  
pp. 610-619 ◽  
Author(s):  
Seunghee Lee ◽  
Dae-Hwan Kim ◽  
Young Hwa Goo ◽  
Young Chul Lee ◽  
Soo-Kyung Lee ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Chromatin Remodeling ◽  
Target Genes ◽  
Mutational Analysis ◽  
Specific Protein ◽  
Transcriptional Coactivator ◽  
Set Domain ◽  
Protein Protein Interaction ◽  
Terminal Set ◽  
Chromatin Remodeling Complex

Abstract Nuclear receptor (NR) transactivation involves multiple coactivators, and the molecular basis for how these are functionally integrated needs to be determined to fully understand the NR action. Activating signal cointegrator-2 (ASC-2), a transcriptional coactivator of many NRs and transcription factors, forms a steady-state complex, ASCOM (for ASC-2 complex), which contains histone H3-lysine-4 (H3K4) methyltransferase MLL3 or its paralog MLL4. Here, we show that ASCOM requires a functional cross talk with the ATPase-dependent chromatin remodeling complex Swi/Snf for efficient NR transactivation. Our results reveal that ASCOM and Swi/Snf are tightly colocalized in the nucleus and that ASCOM and Swi/Snf promote each other’s binding to NR target genes. We further show that the C-terminal SET domain of MLL3 and MLL4 directly interacts with INI1, an integral subunit of Swi/Snf. Our mutational analysis demonstrates that this interaction underlies the mutual facilitation of ASCOM and Swi/Snf recruitment to NR target genes. Importantly, this study uncovers a specific protein-protein interaction as a novel venue to couple two distinct enzymatic coactivator complexes during NR transactivation.

scholarly journals Concerted localization-resets precede YAP-dependent transcription

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
J. Matthew Franklin ◽  
Rajarshi P. Ghosh ◽  
Quanming Shi ◽  
Michael P. Reddick ◽  
Jan T. Liphardt
Keyword(s):  
Transcriptional Activation ◽  
Target Gene ◽  
Target Genes ◽  
Size Control ◽  
Nucleocytoplasmic Shuttling ◽  
Cell Localization ◽  
Actomyosin Contractility ◽  
Real Time Visualization ◽  
Transformed Cell Lines ◽  
Target Gene Transcription

Abstract Yes-associated protein 1 (YAP) is a transcriptional regulator with critical roles in mechanotransduction, organ size control, and regeneration. Here, using advanced tools for real-time visualization of native YAP and target gene transcription dynamics, we show that a cycle of fast exodus of nuclear YAP to the cytoplasm followed by fast reentry to the nucleus (“localization-resets”) activates YAP target genes. These “resets” are induced by calcium signaling, modulation of actomyosin contractility, or mitosis. Using nascent-transcription reporter knock-ins of YAP target genes, we show a strict association between these resets and downstream transcription. Oncogenically-transformed cell lines lack localization-resets and instead show dramatically elevated rates of nucleocytoplasmic shuttling of YAP, suggesting an escape from compartmentalization-based control. The single-cell localization and transcription traces suggest that YAP activity is not a simple linear function of nuclear enrichment and point to a model of transcriptional activation based on nucleocytoplasmic exchange properties of YAP.

scholarly journals abdominal A specifies one cell type in Drosophila by regulating one principal target gene

Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2957-2963 ◽  
Author(s):  
Véronique Brodu ◽  
Philip R. Elstob ◽  
Alex P. Gould
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Hox Genes ◽  
Egf Receptor ◽  
Homeotic Genes ◽  
Unresolved Issue ◽  
Cell Type ◽  
Processing Factor ◽  
Receptor Ligand ◽  
Mutant Rescue

The Hox/homeotic genes encode transcription factors that generate segmental diversity during Drosophila development. At the level of the whole animal, they are believed to carry out this role by regulating a large number of downstream genes. Here we address the unresolved issue of how many Hox target genes are sufficient to define the identity of a single cell. We focus on the larval oenocyte, which is restricted to the abdomen and induced in response to a non-cell autonomous, transient and highly selective input from abdominal A (abdA). We use Hox mutant rescue assays to demonstrate that this function of abdA can be reconstituted by providing Rhomboid (Rho), a processing factor for the EGF receptor ligand, secreted Spitz. Thus, in order to make an oenocyte, abdA regulates just one principal target, rho, that acts at the top of a complex hierarchy of cell-differentiation genes. These studies strongly suggest that, in at least some contexts, Hox genes directly control only a few functional targets within each nucleus. This raises the possibility that much of the overall Hox downstream complexity results from cascades of indirect regulation and cell-to-cell heterogeneity.

scholarly journals Concerted localization-resets precede YAP-dependent transcription

2019 ◽  
Author(s):  
Rajarshi P. Ghosh ◽  
J. Matthew Franklin ◽  
Quanming Shi ◽  
Michael P. Reddick ◽  
Jan T. Liphardt
Keyword(s):  
Transcriptional Activation ◽  
Target Gene ◽  
Target Genes ◽  
Size Control ◽  
Nucleocytoplasmic Shuttling ◽  
Cell Localization ◽  
Actomyosin Contractility ◽  
Real Time Visualization ◽  
Transformed Cell Lines ◽  
Target Gene Transcription

Yes-associated protein 1 (YAP) is a transcriptional regulator with critical roles in mechanotransduction, organ size control, and regeneration. Here, using new tools for real-time visualization of native YAP and target gene transcription dynamics, we show that a cycle of fast exodus of nuclear YAP to the cytoplasm followed by fast reentry to the nucleus (“localization-resets”) activates YAP target genes. These “resets” could be induced by calcium signaling, modulation of actomyosin contractility, or mitosis. Using nascent-transcription reporter knock-ins of YAP target genes, we observed a strict association between these resets and downstream transcription. Oncogenically-transformed transformed cell lines lacked localization-resets and instead showed dramatically elevated rates of nucleocytoplasmic shuttling of YAP, suggesting an escape from compartmentalization-based control. The single-cell localization and transcription traces suggest that YAP activity is not a simple linear function of nuclear enrichment and point to a new model of transcriptional activation based on nucleocytoplasmic exchange properties of YAP.

scholarly journals Identification of homeotic target genes in Drosophila melanogaster including nervy, a proto-oncogene homologue.

Genetics ◽  
1995 ◽  
Vol 140 (2) ◽  
pp. 573-586 ◽  
Author(s):  
P G Feinstein ◽  
K Kornfeld ◽  
D S Hogness ◽  
R S Mann
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Target Genes ◽  
Early Stage ◽  
Gene Expression Pattern ◽  
Morphological Characteristics ◽  
Subtractive Hybridization ◽  
Homeotic Genes ◽  
Target Gene Expression ◽  
Downstream Target

Abstract In Drosophila, the specific morphological characteristics of each segment are determined by the homeotic genes that regulate the expression of downstream target genes. We used a subtractive hybridization procedure to isolate activated target genes of the homeotic gene Ultrabithorax (Ubx). In addition, we constructed a set of mutant genotypes that measures the regulatory contribution of individual homeotic genes to a complex target gene expression pattern. Using these mutants, we demonstrate that homeotic genes can regulate target gene expression at the start of gastrulation, suggesting a previously unknown role for the homeotic genes at this early stage. We also show that, in abdominal segments, the levels of expression for two target genes increase in response to high levels of Ubx, demonstrating that the normal down-regulation of Ubx in these segments is functional. Finally, the DNA sequence of cDNAs for one of these genes predicts a protein that is similar to a human proto-oncogene involved in acute myeloid leukemias. These results illustrate potentially general rules about the homeotic control of target gene expression and suggest that subtractive hybridization can be used to isolate interesting homeotic target genes.

scholarly journals RIP-Seq of EZH2 Identifies TCONS-00036665 as a Regulator of Myogenesis in Pigs

2021 ◽  
Vol 8 ◽  
Author(s):  
Shanshan Wang ◽  
Xuewen Xu ◽  
Yan Liu ◽  
Jianjun Jin ◽  
Feng Zhu ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Histone H3 ◽  
Mechanistic Studies ◽  
Set Domain ◽  
Polycomb Repressive Complex 2 ◽  
Rna Transcripts ◽  
Non Coding Rna ◽  
Rna Immunoprecipitation

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 and contains a SET domain that catalyzes histone H3 trimethylation on lysine 27 (H3K27me3) to generate an epigenetic silencing mark. EZH2 interacts with transcription factors or RNA transcripts to perform its function. In this study, we applied RNA immunoprecipitation sequencing and long intergenic non-coding RNA (lincRNA) sequencing methods to identify EZH2-binding lincRNAs. A total of 356 novel EZH2-binding lincRNAs were identified by bioinformatics analysis and an EZH2-binding lincRNA TCONS-00036665 was characterized. TCONS-00036665 promoted pig skeletal satellite cell proliferation but inhibited cell differentiation, and this function was conserved between pigs and mice. Further mechanistic studies indicated that TCONS-00036665 can bind to EZH2 and recruits EZH2 to the promoters of the target genes p21, MyoG, and Myh4, which leads to the enrichment of H3K27me3 and the repression of target gene expression and pig myogenesis. In conclusion, the lincRNA TCONS-00036665 regulates pig myogenesis through its interaction with EZH2.

Sign in / Sign up

Export Citation Format

Share Document