scholarly journals Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors

Development ◽  
2018 ◽  
Vol 145 (7) ◽  
pp. dev161208 ◽  
Author(s):  
Mickael Orgeur ◽  
Marvin Martens ◽  
Georgeta Leonte ◽  
Sonya Nassari ◽  
Marie-Ange Bonnin ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Connective Tissue ◽  
Target Genes ◽  
Downstream Target ◽  
Genome Wide

scholarly journals A role for Arabidopsis growth-regulating factors 1 and 3 in growth–stress antagonism

2019 ◽  
Vol 71 (4) ◽  
pp. 1402-1417 ◽  
Author(s):  
Sarbottam Piya ◽  
Jinyi Liu ◽  
Tessa Burch-Smith ◽  
Thomas J Baum ◽  
Tarek Hewezi
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Growth Stress ◽  
Plant Responses ◽  
Chip Sequencing ◽  
Downstream Target ◽  
Genome Wide ◽  
Abiotic Stimuli ◽  
Regulatory Functions ◽  
Core Genes

Abstract Growth-regulating factors (GRFs) belong to a small family of transcription factors that are highly conserved in plants. GRFs regulate many developmental processes and plant responses to biotic and abiotic stimuli. Despite the importance of GRFs, a detailed mechanistic understanding of their regulatory functions is still lacking. In this study, we used ChIP sequencing (ChIP-seq) to identify genome-wide binding sites of Arabidopsis GRF1 and GRF3, and correspondingly their direct downstream target genes. RNA-sequencing (RNA-seq) analysis revealed that GRF1 and GRF3 regulate the expression of a significant number of the identified direct targets. The target genes unveiled broad regulatory functions of GRF1 and GRF3 in plant growth and development, phytohormone biosynthesis and signaling, and the cell cycle. Our analyses also revealed that clock core genes and genes with stress- and defense-related functions are most predominant among the GRF1- and GRF3-bound targets, providing insights into a possible role for these transcription factors in mediating growth–defense antagonism and integrating environmental stimuli into developmental programs. Additionally, GRF1 and GRF3 target molecular nodes of growth–defense antagonism and modulate the levels of defense- and development-related hormones in opposite directions. Taken together, our results point to GRF1 and GRF3 as potential key determinants of plant fitness under stress conditions.

Drosophila Gain-of-Function Mutant RTK Torso Triggers Ectopic Dpp and STAT Signaling

Genetics ◽  
2003 ◽  
Vol 164 (1) ◽  
pp. 247-258 ◽  
Author(s):  
Jinghong Li ◽  
Willis X Li
Keyword(s):  
Tyrosine Kinases ◽  
Target Genes ◽  
Tor Signaling ◽  
Gain Of Function ◽  
Essential Requirement ◽  
Downstream Target ◽  
Rtk Signaling ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

Abstract Overactivation of receptor tyrosine kinases (RTKs) has been linked to tumorigenesis. To understand how a hyperactivated RTK functions differently from wild-type RTK, we conducted a genome-wide systematic survey for genes that are required for signaling by a gain-of-function mutant Drosophila RTK Torso (Tor). We screened chromosomal deficiencies for suppression of a gain-of-function mutation tor (torGOF), which led to the identification of 26 genomic regions that, when in half dosage, suppressed the defects caused by torGOF. Testing of candidate genes in these regions revealed many genes known to be involved in Tor signaling (such as those encoding the Ras-MAPK cassette, adaptor and structural molecules of RTK signaling, and downstream target genes of Tor), confirming the specificity of this genetic screen. Importantly, this screen also identified components of the TGFβ (Dpp) and JAK/STAT pathways as being required for TorGOF signaling. Specifically, we found that reducing the dosage of thickveins (tkv), Mothers against dpp (Mad), or STAT92E (aka marelle), respectively, suppressed torGOF phenotypes. Furthermore, we demonstrate that in torGOF embryos, dpp is ectopically expressed and thus may contribute to the patterning defects. These results demonstrate an essential requirement of noncanonical signaling pathways for a persistently activated RTK to cause pathological defects in an organism.

scholarly journals Cell transformation mediated by homodimeric E2A-HLF transcription factors.

1997 ◽  
Vol 17 (3) ◽  
pp. 1417-1424 ◽  
Author(s):  
T Inukai ◽  
T Inaba ◽  
T Yoshihara ◽  
A T Look
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Fusion Gene ◽  
Dominant Negative ◽  
Fusion Product ◽  
3T3 Cells ◽  
Par Proteins ◽  
Downstream Target ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

The E2A-HLF fusion gene, created by the t(17;19)(q22;p13) chromosomal translocation in pro-B lymphocytes, encodes an oncogenic protein in which the E2A trans-activation domain is linked to the DNA-binding and protein dimerization domain of hepatic leukemia factor (HLF), a member of the proline- and acidic amino acid-rich (PAR) subfamily of bZIP transcription factors. This fusion product binds to its DNA recognition site not only as a homodimer but also as a heterodimer with HLF and two other members of the PAR bZIP subfamily, thyrotroph embryonic factor (TEF) and albumin promoter D-box binding protein (DBP). Thus, E2A-HLF could transform cells by direct regulation of downstream target genes, acting through homodimeric or heterodimeric complexes, or by sequestering normal PAR proteins into nonfunctional heterocomplexes (dominant-negative interference). To distinguish among these models, we constructed mutant E2A-HLF proteins in which the leucine zipper domain of HLF was extended by one helical turn or altered in critical charged amino acids, enabling the chimera to bind to DNA as a homodimer but not as a heterodimer with HLF or other PAR proteins. When introduced into NIH 3T3 cells in a zinc-inducible vector, each of these mutants induced anchorage-independent growth as efficiently as unaltered E2A-HLF, indicating that the chimeric oncoprotein can transform cells in its homodimeric form. Transformation also depended on an intact E2A activator region, providing further support for a gain-of-function contribution to oncogenesis rather than one based on a dominant-interfering or dominant-negative mechanism. Thus, the tumorigenic effects of E2A-HLF and its mutant forms in NIH 3T3 cells favor a straightforward model in which E2A-HLF homodimers bind directly to promoter/enhancer elements of downstream target genes and alter their patterns of expression in early B-cell progenitors.

scholarly journals Potential Downstream Target Genes of Aberrant ETS Transcription Factors Are Differentially Affected in Ewing’s Sarcoma and Prostate Carcinoma

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49819 ◽  
Author(s):  
Maria J. Camões ◽  
Paula Paulo ◽  
Franclim R. Ribeiro ◽  
João D. Barros-Silva ◽  
Mafalda Almeida ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Prostate Carcinoma ◽  
Target Genes ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Ets Transcription Factors ◽  
Downstream Target

Regulation and function of homeodomain proteins in the embryonic and adult vascular systemsThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigators' Forum.

2007 ◽  
Vol 85 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Josette M. Douville ◽  
Jeffrey T. Wigle
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Vascular System ◽  
Homeobox Genes ◽  
Tube Formation ◽  
Binding Motif ◽  
Homeodomain Proteins ◽  
Downstream Target ◽  
Endothelial Tube Formation ◽  
And Function

During embryonic development, the cardiovascular system first forms and then gives rise to the lymphatic vascular system. Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. These genes all encode proteins that are transcription factors that contain a well conserved DNA binding motif, the homeodomain. It is through the homeodomain that these transcription factors bind to the promoters of target genes and regulate their expression. Although many homeodomain proteins have been found to be expressed within the vascular systems, little is known about their downstream target genes. This review highlights recent advances made in the identification of novel genes downstream of the homeodomain proteins that are necessary for regulating vascular cellular processes such as proliferation, migration, and endothelial tube formation. Factors known to regulate the functions of vascular cells via modulating the expression of homeobox genes will be discussed. We will also review current methods used to identify and characterize downstream target genes of homeodomain proteins.

scholarly journals Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

2010 ◽  
Vol 162 (3) ◽  
pp. 625-631 ◽  
Author(s):  
Jonna Salonen ◽  
Ewa Rajpert-De Meyts ◽  
Susanna Mannisto ◽  
John E Nielsen ◽  
Niels Graem ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Germ Cell ◽  
Germ Cells ◽  
Target Genes ◽  
Developmental Expression ◽  
Human Testis ◽  
Testicular Development ◽  
Downstream Target ◽  
Germ Cell Differentiation

ObjectiveTesticular germ cell cancer is the most common malignancy among young males. The pre-invasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms.MethodsFetal testis, testicular CIS, and overt tumor samples were analyzed by immunohistochemistry for GATA-4, GATA-6, FOG-2, steroidogenic factor 1 (NR5A1/SF1), anti-Müllerian hormone/Müllerian-inhibiting substance (AMH), and inhibin-α (INHα).ResultsGATA-4 was not expressed in normal germ cells, except for a subset of gonocytes at the 15th gestational week. The CIS cells expressed GATA-4 and GATA-6 heterogeneously, whereas most of the CIS cells expressed GATA-4 cofactor FOG-2. GATA target gene SF-1 was expressed heterogeneously in CIS cells, whereas INHα and AMH were mostly negative. Seminomas and yolk sac tumors were positive for GATA-4 and GATA-6, but mostly negative for FOG-2 and the GATA target genes. In contrast, pluripotent embryonal carcinomas and choriocarcinomas were GATA-4 and GATA-6 negative.ConclusionsDifferential expression of the GATA-4 target genes suggested cell-specific functions of GATA-4 in the germ and somatic cells. The GATA-4 expression in early fetal gonocytes, CIS, and seminoma cells but the absence in more mature germ cells is consistent with the early fetal origin of CIS cells and suggests that GATA-4 is involved in early germ cell differentiation.

scholarly journals EAT-UpTF: Enrichment Analysis Tool for Upstream Transcription Fctors of a gene group

2020 ◽  
Author(s):  
Sangrea Shim ◽  
Pil Joon Seo
Keyword(s):  
Transcription Factors ◽  
Open Source ◽  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Affinity Purification ◽  
Enrichment Analysis ◽  
Analysis Tool ◽  
Gene Group ◽  
Genome Wide ◽  
One Step

SummaryEAT-UpTF (Enrichment Analysis Tool for Upstream Transcription Factors of a gene group) is an open-source Python script that analyzes the enrichment of upstream transcription factors (TFs) in a group of genes-of-interest (GOIs). EAT-UpTF utilizes genome-wide lists of TF-target genes generated by DNA affinity purification followed by sequencing (DAP-seq) or chromatin immunoprecipitation followed by sequencing (ChIP-seq). Unlike previous methods based on the two-step prediction of cis-motifs and DNA-element-binding TFs, our EAT-UpTF analysis enabled a one-step identification of enriched upstream TFs in a set of GOIs using lists of empirically determined TF-target [email protected] or [email protected]://github.com/sangreashim/EAT-UpTF

scholarly journals Oncogenic Notch promotes long-range regulatory interactions within hyperconnected 3D cliques

2019 ◽  
Author(s):  
Jelena Petrovic ◽  
Yeqiao Zhou ◽  
Maria Fasolino ◽  
Naomi Goldman ◽  
Gregory W. Schwartz ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Long Range ◽  
Spatial Organization ◽  
Target Genes ◽  
Large Fraction ◽  
B Cell Lymphoma ◽  
3 Dimensional ◽  
Regulatory Interactions ◽  
Genome Wide ◽  
Target Promoters

AbstractChromatin loops enable transcription factor-bound distal enhancers to interact with their target promoters to regulate transcriptional programs. Although developmental transcription factors, such as active forms of Notch, can directly stimulate transcription by activating enhancers, the effect of their oncogenic subversion on the 3-dimensional (3D) organization of the cancer genome is largely undetermined. By mapping chromatin looping genome-wide in Notch-dependent triple-negative breast cancer and B-cell lymphoma, we show that far beyond the well-characterized role of Notch as an activator of distal enhancers, Notch regulates its direct target genes through establishing new long-range regulatory interactions. Moreover, a large fraction of Notch-promoted regulatory loops forms highly interacting enhancer and promoter spatial clusters, termed “3D cliques”. Loss-and gain-of-function experiments show that Notch preferentially targets hyperconnected 3D cliques that regulate the expression of crucial proto-oncogenes. Our observations suggest that oncogenic hijacking of developmental transcription factors can dysregulate transcription through widespread effects on the spatial organization of cancer genomes.

scholarly journals Genome-wide reduction in chromatin accessibility and unique transcription factor footprints in endothelial cells and fibroblasts in scleroderma skin

2020 ◽  
Author(s):  
Pei-Suen Tsou ◽  
Pamela J. Palisoc ◽  
Mustafa Ali ◽  
Dinesh Khanna ◽  
Amr H Sawalha
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Target Genes ◽  
Critical Role ◽  
Vascular Complications ◽  
Chromatin Accessibility ◽  
Unknown Etiology ◽  
Healthy Controls ◽  
Genome Wide

AbstractSystemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by widespread fibrosis and vascular complications. We utilized an assay for genome-wide chromatin accessibility to examine the chromatin landscape and transcription factor footprints in both endothelial cells (ECs) and fibroblasts isolated from healthy controls and patients with diffuse cutaneous (dc) SSc. In both cell types, chromatin accessibility was significantly reduced in SSc patients compared to healthy controls. Genes annotated from differentially accessible chromatin regions were enriched in pathways and gene ontologies involved in the nervous system. In addition, our data revealed that chromatin binding of transcription factors SNAI2, ETV2, and ELF1 was significantly increased in dcSSc ECs, while recruitment of RUNX1 and RUNX2 was enriched in dcSSc fibroblasts. Significant elevation of SNAI2 and ETV2 levels in dcSSc ECs, and RUNX2 levels in dcSSc fibroblasts were confirmed. Further analysis of publicly available ETV2-target genes suggests that ETV2 may play a critical role in EC dysfunction in dcSSc. Our data, for the first time, uncovered the chromatin blueprint of dcSSc ECs and fibroblasts, and suggested that neural-related characteristics of SSc ECs and fibroblasts could be a culprit for dysregulated angiogenesis and enhanced fibrosis. Targeting these pathways and the key transcription factors identified might present novel therapeutic approaches for this disease.

Sign in / Sign up

Export Citation Format

Share Document