Regulation of the ANF and BNP promoters by GATA factors: Lessons learned for cardiac transcription

2001 ◽  
Vol 79 (8) ◽  
pp. 673-681 ◽  
Author(s):  
Kevin McBride ◽  
Mona Nemer

The identification and molecular cloning of the cardiac transcription factors GATA-4, -5, and -6 has greatly contributed to our understanding of how tissue-specific transcription is achieved during cardiac growth and development. Through analysis of their interacting partners, it has also become apparent that a major mechanism underlying spatial and temporal specificity within the heart as well as in the response to cardiogenic regulators is the combinatorial interaction between cardiac-restricted and inducible transcription factors. The cardiac GATA factors appear to be fundamental contributors to these regulatory networks. Two of the first targets identified for the cardiac GATA factors were the natriuretic peptide genes encoding atrial natriuretic factor (ANF) and B-type natriuretic peptide (BNP), the major heart secretory products that are also accepted clinical markers of the diseased heart. Studies using the ANF and BNP promoters as models of cardiac-specific transcription have unraveled the pivotal role that GATA proteins play in cardiac gene expression. We review the current knowledge on the modulation of the natriuretic peptide promoters by GATA factors, including examples of combinatorial interactions between GATA proteins and diverse transcription factors.Key words: ANF, BNP, GATA factors, cardiac transcription.

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 299
Author(s):  
Takashi Moriguchi

The GATA family of transcription factors consists of six proteins (GATA1-6) that control a variety of physiological and pathological processes. In particular, GATA2 and GATA3 are coexpressed in a number of tissues, including in the urogenital and sympathoadrenal systems, in which both factors participate in the developmental process and tissue maintenance. Furthermore, accumulating studies have demonstrated that GATA2 and GATA3 are involved in distinct types of inherited diseases as well as carcinogenesis in diverse tissues. This review summarizes our current knowledge of how GATA2 and GATA3 participate in the transcriptional regulatory circuitry during the development of the sympathoadrenal and urogenital systems, and how their dysregulation results in the carcinogenesis of neuroblastoma, renal urothelial, and gynecologic cancers.


2019 ◽  
Vol 18 ◽  
pp. 117693511985986 ◽  
Author(s):  
Salam A Assi ◽  
Constanze Bonifer ◽  
Peter N Cockerill

Acute myeloid leukemia (AML) is a highly heterogeneous cancer associated with different patterns of gene expression determined by the nature of their DNA mutations. These mutations mostly act to deregulate gene expression by various mechanisms at the level of the nucleus. By performing genome-wide epigenetic profiling of cis-regulatory elements, we found that AML encompasses different mutation-specific subclasses associated with the rewiring of the gene regulatory networks that drive differentiation into different directions away from normal myeloid development. By integrating epigenetic profiles with gene expression and chromatin conformation data, we defined pathways within gene regulation networks that were differentially rewired within each mutation-specific subclass of AML. This analysis revealed 2 major classes of AML: one class defined by mutations in signaling molecules that activate AP-1 via the mitogen-activated protein (MAP) kinase pathway and a second class defined by mutations within genes encoding transcription factors such as RUNX1/CBFβ and C/EBPα. By identifying specific DNA motifs protected from DNase I digestion at cis-regulatory elements, we were able to infer candidate transcription factors bound to these motifs. These integrated analyses allowed the identification of AML subtype-specific core regulatory networks that are required for AML development and maintenance, which could now be targeted in personalized therapies.


2020 ◽  
Vol 21 (18) ◽  
pp. 6513 ◽  
Author(s):  
Shubhra Acharya ◽  
Antonio Salgado-Somoza ◽  
Francesca Maria Stefanizzi ◽  
Andrew I. Lumley ◽  
Lu Zhang ◽  
...  

Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.


2006 ◽  
Vol 8 (22) ◽  
pp. 1-20 ◽  
Author(s):  
Alison Brewer ◽  
John Pizzey

Vertebrate heart formation is dependent upon complex hierarchical gene regulatory networks, which effect both the specification and differentiation of cardiomyocytes and subsequently cardiac morphogenesis. GATA-4, -5 and -6 comprise an evolutionarily conserved subfamily of transcription factors, which are expressed within the precardiac mesoderm from early stages in its specification and continue to be expressed within the adult heart. We review here the functional roles of individual GATA transcription factors in cardiac development, normal homeostasis and disease. We also review the cellular mechanisms employed to regulate the expression and downstream targets of the different GATA factors.


2014 ◽  
Vol 306 (6) ◽  
pp. G474-G490 ◽  
Author(s):  
Boaz E. Aronson ◽  
Kelly A. Stapleton ◽  
Stephen D. Krasinski

The small intestinal epithelium develops from embryonic endoderm into a highly specialized layer of cells perfectly suited for the digestion and absorption of nutrients. The development, differentiation, and regeneration of the small intestinal epithelium require complex gene regulatory networks involving multiple context-specific transcription factors. The evolutionarily conserved GATA family of transcription factors, well known for its role in hematopoiesis, is essential for the development of endoderm during embryogenesis and the renewal of the differentiated epithelium in the mature gut. We review the role of GATA factors in the evolution and development of endoderm and summarize our current understanding of the function of GATA factors in the mature small intestine. We offer perspective on the application of epigenetics approaches to define the mechanisms underlying context-specific GATA gene regulation during intestinal development.


Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 142 ◽  
Author(s):  
Alejandro Piña-Iturbe ◽  
Isidora D. Suazo ◽  
Guillermo Hoppe-Elsholz ◽  
Diego Ulloa-Allendes ◽  
Pablo A. González ◽  
...  

Acquisition of mobile elements by horizontal gene transfer can play a major role in bacterial adaptation and genome evolution by providing traits that contribute to bacterial fitness. However, gaining foreign DNA can also impose significant fitness costs to the host bacteria and can even produce detrimental effects. The efficiency of horizontal acquisition of DNA is thought to be improved by the activity of xenogeneic silencers. These molecules are a functionally related group of proteins that possess affinity for the acquired DNA. Binding of xenogeneic silencers suppresses the otherwise uncontrolled expression of genes from the newly acquired nucleic acid, facilitating their integration to the bacterial regulatory networks. Even when the genes encoding for xenogeneic silencers are part of the core genome, homologs encoded by horizontally acquired elements have also been identified and studied. In this article, we discuss the current knowledge about horizontally acquired xenogeneic silencer homologs, focusing on those encoded by genomic islands, highlighting their distribution and the major traits that allow these proteins to become part of the host regulatory networks.


Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2681
Author(s):  
Sophie Kellaway ◽  
Paulynn S. Chin ◽  
Farnaz Barneh ◽  
Constanze Bonifer ◽  
Olaf Heidenreich

Acute myeloid leukemia (AML) is a heterogenous disease with multiple sub-types which are defined by different somatic mutations that cause blood cell differentiation to go astray. Mutations occur in genes encoding members of the cellular machinery controlling transcription and chromatin structure, including transcription factors, chromatin modifiers, DNA-methyltransferases, but also signaling molecules that activate inducible transcription factors controlling gene expression and cell growth. Mutant cells in AML patients are unable to differentiate and adopt new identities that are shaped by the original driver mutation and by rewiring their gene regulatory networks into regulatory phenotypes with enhanced fitness. One of the best-studied AML-subtypes is the t(8;21) AML which carries a translocation fusing sequences encoding the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO gene. The resulting oncoprotein, RUNX1/ETO has been studied for decades, both at the biochemical but also at the systems biology level. It functions as a dominant-negative version of RUNX1 and interferes with multiple cellular processes associated with myeloid differentiation, growth regulation and genome stability. In this review, we summarize our current knowledge of how this protein reprograms normal into malignant cells and how our current knowledge could be harnessed to treat the disease.


2020 ◽  
Author(s):  
Leandro Murgas ◽  
Sebastian Contreras-Riquelme ◽  
J. Eduardo Martínez ◽  
Camilo Villaman ◽  
Rodrigo Santibáñez ◽  
...  

AbstractMotivationThe regulation of gene expression is a key factor in the development and maintenance of life in all organisms. This process is carried out mainly through the action of transcription factors (TFs), although other actors such as ncRNAs are involved. In this work, we propose a new method to construct Gene Regulatory Networks (GRNs) depicting regulatory events in a certain context for Drosophila melanogaster. Our approach is based on known relationships between epigenetics and the activity of transcription factors.ResultsWe developed method, Tool for Weighted Epigenomic Networks in D. melanogaster (Fly T-WEoN), which generates GRNs starting from a reference network that contains all known gene regulations in the fly. Regulations that are unlikely taking place are removed by applying a series of knowledge-based filters. Each of these filters is implemented as an independent module that considers a type of experimental evidence, including DNA methylation, chromatin accessibility, histone modifications, and gene expression. Fly T-WEoN is based on heuristic rules that reflect current knowledge on gene regulation in D. melanogaster obtained from literature. Experimental data files can be generated with several standard procedures and used solely when and if available.Fly T-WEoN is available as a Cytoscape application that permits integration with other tools, and facilitates downstream network analysis. In this work, we first demonstrate the reliability of our method to then provide a relevant application case of our tool: early development of D. melanogaster.AvailabilityFly T-WEoN, together with its step-by-step guide is available at https://[email protected]


2021 ◽  
Vol 22 (11) ◽  
pp. 5949
Author(s):  
Yuli Zhang ◽  
Linlin Hou

Sox proteins are known as crucial transcription factors for many developmental processes and for a wide range of common diseases. They were believed to specifically bind and bend DNA with other transcription factors and elicit transcriptional activation or repression activities in the early stage of transcription. However, their functions are not limited to transcription initiation. It has been showed that Sox proteins are involved in the regulation of alternative splicing regulatory networks and translational control. In this review, we discuss the current knowledge on how Sox transcription factors such as Sox2, Sry, Sox6, and Sox9 allow the coordination of co-transcriptional splicing and also the mechanism of SOX4-mediated translational control in the context of RNA polymerase III.


Plants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1014
Author(s):  
Jun He ◽  
Harro J. Bouwmeester ◽  
Marcel Dicke ◽  
Iris F. Kappers

To gain insight into the regulatory networks that underlie the induced defense in cucumber against spider mites, genes encoding transcription factors (TFs) were identified in the cucumber (Cucumissativus) genome and their regulation by two-spotted spider mite (Tetranychusurticae) herbivory was analyzed using RNA-seq. Of the total 1212 annotated TF genes in the cucumber genome, 119 were differentially regulated upon spider-mite herbivory during a period of 3 days. These TF genes belong to different categories but the MYB, bHLH, AP2/ERF and WRKY families had the highest relative numbers of differentially expressed genes. Correlation analysis of the expression of TF genes with defense-associated genes during herbivory and pathogen infestation, and in different organs resulted in the putative identification of regulators of herbivore-induced terpenoid and green-leaf-volatile biosynthesis. Analysis of the cis-acting regulatory elements (CAREs) present in the promoter regions of the genes responsive to spider-mite feeding revealed potential TF regulators. This study describes the TF genes in cucumber that are potentially involved in the regulation of induced defense against herbivory by spider mites.


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