scholarly journals Sociosexual behavior requires both activating and repressive roles of Tfap2e/AP-2ε in vomeronasal sensory neurons

2022 ◽  
Author(s):  
Jennifer M Lin ◽  
Tyler A Mitchell ◽  
Megan Rothstein ◽  
Alison Pehl ◽  
Ed Zandro M Taroc ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Sensory Neurons ◽  
Neurodegenerative Disorders ◽  
Molecular Mechanisms ◽  
Vomeronasal Organ ◽  
Neuronal Identity ◽  
Sociosexual Behavior ◽  
Unique System ◽  
Cellular Identity

Neuronal identity dictates the position in an epithelium, and the ability to detect, process, and transmit specific signals to specified targets. Transcription factors (TFs) determine cellular identity via direct modulation of genetic transcription and recruiting chromatin modifiers. However, our understanding of the mechanisms that define neuronal identity and their magnitude remains a critical barrier to elucidate the etiology of congenital and neurodegenerative disorders. The rodent vomeronasal organ provides a unique system to examine in detail the molecular mechanisms underlying the differentiation and maturation of chemosensory neurons. Here we demonstrated that the identity of postmitotic/maturing VSNs and vomeronasal dependent behaviors can be reprogrammed through the rescue of AP-2ε expression in the AP-2ε Null mice and by inducing ectopic AP-2ε expression in mature apical VSNs. We suggest that the transcription factor AP-2ε can reprogram VSNs bypassing cellular plasticity restrictions, and that it directly controls the expression of batteries of vomeronasal genes.

scholarly journals Transcriptional Regulation of the Gene Encoding an Alcohol Dehydrogenase in the Archaeon Sulfolobus solfataricus Involves Multiple Factors and Control Elements

2003 ◽  
Vol 185 (13) ◽  
pp. 3926-3934 ◽  
Author(s):  
Gabriella Fiorentino ◽  
Raffaele Cannio ◽  
Mosè Rossi ◽  
Simonetta Bartolucci
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Alcohol Dehydrogenase ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Sulfolobus Solfataricus ◽  
Regulatory Sequences ◽  
Mobility Shift ◽  
Tata Element ◽  
Responsive Element

ABSTRACT A transcriptionally active region has been identified in the 5′ flanking region of the alcohol dehydrogenase gene of the crenarchaeon Sulfolobus solfataricus through the evaluation of the activity of putative transcriptional regulators and the role of the region upstream of the gene under specific metabolic circumstances. Electrophoretic mobility shift assays with crude extracts revealed protein complexes that most likely contain TATA box-associated factors. When the TATA element was deleted from the region, binding sites for both DNA binding proteins, such as the small chromatin structure-modeling Sso7d and Sso10b (Alba), and transcription factors, such as the repressor Lrs14, were revealed. To understand the molecular mechanisms underlying the substrate-induced expression of the adh gene, the promoter was analyzed for the presence of cis-acting elements recognized by specific transcription factors upon exposure of the cell to benzaldehyde. Progressive dissection of the identified promoter region restricted the analysis to a minimal responsive element (PAL) located immediately upstream of the transcription factor B-responsive element-TATA element, resembling typical bacterial regulatory sequences. A benzaldehyde-activated transcription factor (Bald) that specifically binds to the PAL cis-acting element was also identified. This protein was purified from heparin-fractionated extracts of benzaldehyde-induced cells and was shown to have a molecular mass of ∼16 kDa. The correlation between S. solfataricus adh gene activation and benzaldehyde-inducible occupation of a specific DNA sequence in its promoter suggests that a molecular signaling mechanism is responsible for the switch of the aromatic aldehyde metabolism as a response to environmental changes.

scholarly journals Heterologous Expression of Transcription Factor AtWRKY57 Alleviates Salt Stress-Induced Oxidative Damage

2018 ◽  
Vol 12 (1) ◽  
pp. 204-218
Author(s):  
Wei Tang
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Salt Stress ◽  
Heterologous Expression ◽  
Stress Tolerance ◽  
Molecular Mechanisms ◽  
Abiotic Stress Tolerance ◽  
Thiobarbituric Acid Reactive Substance ◽  
Salt Stress Tolerance ◽  
Wrky Transcription Factors

Background:WRKY transcription factors play important roles in the responses to abiotic stresses, seed dormancy, seed germination, developmental processes, secondary metabolism, and senescence in plants. However, molecular mechanisms of WRKY transcription factors-related abiotic stress tolerance have not been fully understood.Methods:In this investigation, transcription factor AtWRKY57 was introduced into cell lines of rice (Oryza sativaL.), tobacco (Nicotiana tabacum), and white pine (Pinus strobesL.) for characterization of its function in salt stress tolerance. The purpose of this investigation is to examine the function of AtWRKY in a broad sample of plant species including monocotyledons, dicotyledons, and gymnosperms.Results:The experimental results demonstrated that heterologous expression of transcription factor AtWRKY57 improves salt stress tolerance by decreasing Thiobarbituric Acid Reactive Substance (TBARS), increasing Ascorbate Peroxidase (APOX) and Catalase (CAT) activity under salt stress. In rice, overexpression of transcription factor AtWRKY57 enhances expression of Ca2+-dependent protein kinase genesOsCPk6andOsCPk19to counteract salt stress.Conclusion:These results indicated that transcription factor AtWRKY57 might have practical application in genetic engineering of plant salt tolerance throughout the plant kingdom.

scholarly journals Nr4a2 Transcription Factor in Hippocampal Synaptic Plasticity, Memory and Cognitive Dysfunction: A Perspective Review

2021 ◽  
Vol 14 ◽  
Author(s):  
Judit Català-Solsona ◽  
Alfredo J. Miñano-Molina ◽  
José Rodríguez-Álvarez
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Synaptic Plasticity ◽  
Nuclear Receptor ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Memory Formation ◽  
Synaptic Dysfunction ◽  
Hippocampal Synaptic Plasticity

Long-lasting changes of synaptic efficacy are largely mediated by activity-induced gene transcription and are essential for neuronal plasticity and memory. In this scenario, transcription factors have emerged as pivotal players underlying synaptic plasticity and the modification of neural networks required for memory formation and consolidation. Hippocampal synaptic dysfunction is widely accepted to underlie the cognitive decline observed in some neurodegenerative disorders including Alzheimer’s disease. Therefore, understanding the molecular pathways regulating gene expression profiles may help to identify new synaptic therapeutic targets. The nuclear receptor 4A subfamily (Nr4a) of transcription factors has been involved in a variety of physiological processes within the hippocampus, ranging from inflammation to neuroprotection. Recent studies have also pointed out a role for the activity-dependent nuclear receptor subfamily 4, group A, member 2 (Nr4a2/Nurr1) in hippocampal synaptic plasticity and cognitive functions, although the underlying molecular mechanisms are still poorly understood. In this review, we highlight the specific effects of Nr4a2 in hippocampal synaptic plasticity and memory formation and we discuss whether the dysregulation of this transcription factor could contribute to hippocampal synaptic dysfunction, altogether suggesting the possibility that Nr4a2 may emerge as a novel synaptic therapeutic target in brain pathologies associated to cognitive dysfunctions.

scholarly journals The biological characteristics of transcription factors AP-2α and AP-2γ and their importance in various types of cancers

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Damian Kołat ◽  
Żaneta Kałuzińska ◽  
Andrzej K. Bednarek ◽  
Elżbieta Płuciennik
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Cancer Tissue ◽  
Diagnostic Biomarkers ◽  
Oncological Patients ◽  
Wide Range ◽  
Non Coding Rnas

Abstract The Activator Protein 2 (AP-2) transcription factor (TF) family is vital for the regulation of gene expression during early development as well as carcinogenesis process. The review focusses on the AP-2α and AP-2γ proteins and their dualistic regulation of gene expression in the process of carcinogenesis. Both AP-2α and AP-2γ influence a wide range of physiological or pathological processes by regulating different pathways and interacting with diverse molecules, i.e. other proteins, long non-coding RNAs (lncRNA) or miRNAs. This review summarizes the newest information about the biology of two, AP-2α and AP-2γ, TFs in the carcinogenesis process. We emphasize that these two proteins could have either oncogenic or suppressive characteristics depending on the type of cancer tissue or their interaction with specific molecules. They have also been found to contribute to resistance and sensitivity to chemotherapy in oncological patients. A better understanding of molecular network of AP-2 factors and other molecules may clarify the atypical molecular mechanisms occurring during carcinogenesis, and may assist in the recognition of new diagnostic biomarkers.

scholarly journals Differential Requirement of the Transcription Factor Mcm1 for Activation of the Candida albicans Multidrug Efflux PumpMDR1by Its Regulators Mrr1 and Cap1

2011 ◽  
Vol 55 (5) ◽  
pp. 2061-2066 ◽  
Author(s):  
Selene Mogavero ◽  
Arianna Tavanti ◽  
Sonia Senesi ◽  
P. David Rogers ◽  
Joachim Morschhäuser
Keyword(s):  
Transcription Factor ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Gain Of Function ◽  
Pathogenic Yeast ◽  
Content Type

ABSTRACTOverexpression of the multidrug efflux pump Mdr1 causes increased fluconazole resistance in the pathogenic yeastCandida albicans. The transcription factors Mrr1 and Cap1 mediateMDR1upregulation in response to inducing stimuli, and gain-of-function mutations in Mrr1 or Cap1, which render the transcription factors hyperactive, result in constitutiveMDR1overexpression. The essential MADS box transcription factor Mcm1 also binds to theMDR1promoter, but its role in inducible or constitutiveMDR1upregulation is unknown. Using a conditional mutant in which Mcm1 can be depleted from the cells, we investigated the importance of Mcm1 forMDR1expression. We found that Mcm1 was dispensable forMDR1upregulation by H2O2but was required for fullMDR1induction by benomyl. A C-terminally truncated, hyperactive Cap1 could upregulateMDR1expression both in the presence and in the absence of Mcm1. In contrast, a hyperactive Mrr1 containing a gain-of-function mutation depended on Mcm1 to causeMDR1overexpression. These results demonstrate a differential requirement for the coregulator Mcm1 for Cap1- and Mrr1-mediatedMDR1upregulation. When activated by oxidative stress or a gain-of-function mutation, Cap1 can induceMDR1expression independently of Mcm1, whereas Mrr1 requires either Mcm1 or an active Cap1 to cause overexpression of theMDR1efflux pump. Our findings provide more detailed insight into the molecular mechanisms of drug resistance in this important human fungal pathogen.

scholarly journals Landscape of allele-specific transcription factor binding in the human genome

2020 ◽  
Author(s):  
Sergey Abramov ◽  
Alexandr Boytsov ◽  
Dariia Bykova ◽  
Dmitry D. Penzar ◽  
Ivan Yevshin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Specific Binding ◽  
Transcription Factor Binding ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Specific Transcription Factor ◽  
Factor Binding ◽  
Allele Specific

AbstractSequence variants in gene regulatory regions alter gene expression and contribute to phenotypes of individual cells and the whole organism, including disease susceptibility and progression. Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Differential transcription factor binding in heterozygous genomic loci provides a natural source of information on such regulatory variants. We present a novel approach to call the allele-specific transcription factor binding events at single-nucleotide variants in ChIP-Seq data, taking into account the joint contribution of aneuploidy and local copy number variation, that is estimated directly from variant calls. We have conducted a meta-analysis of more than 7 thousand ChIP-Seq experiments and assembled the database of allele-specific binding events listing more than half a million entries at nearly 270 thousand single-nucleotide polymorphisms for several hundred human transcription factors and cell types. These polymorphisms are enriched for associations with phenotypes of medical relevance and often overlap eQTLs, making candidates for causality by linking variants with molecular mechanisms. Specifically, there is a special class of switching sites, where different transcription factors preferably bind alternative alleles, thus revealing allele-specific rewiring of molecular circuitry.

scholarly journals Molecular mechanisms of transcription factor mediated cell reprogramming: conversion of liver to pancreas

2021 ◽  
Author(s):  
Sebastian L. Wild ◽  
David Tosh
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cellular Reprogramming ◽  
Directed Differentiation ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
Cell Type ◽  
Β Cells ◽  
Master Regulator ◽  
Cellular Identity

Transdifferentiation is a type of cellular reprogramming involving the conversion of one differentiated cell type to another. This remarkable phenomenon holds enormous promise for the field of regenerative medicine. Over the last 20 years techniques used to reprogram cells to alternative identities have advanced dramatically. Cellular identity is determined by the transcriptional profile which comprises the subset of mRNAs, and therefore proteins, being expressed by a cell at a given point in time. A better understanding of the levers governing transcription factor activity benefits our ability to generate therapeutic cell types at will. One well-established example of transdifferentiation is the conversion of hepatocytes to pancreatic β-cells. This cell type conversion potentially represents a novel therapy in T1D treatment. The identification of key master regulator transcription factors (which distinguish one body part from another) during embryonic development has been central in developing transdifferentiation protocols. Pdx1 is one such example of a master regulator. Ectopic expression of vector-delivered transcription factors (particularly the triumvirate of Pdx1, Ngn3 and MafA) induces reprogramming through broad transcriptional remodelling. Increasingly, complimentary cell culture techniques, which recapitulate the developmental microenvironment, are employed to coax cells to adopt new identities by indirectly regulating transcription factor activity via intracellular signalling pathways. Both transcription factor-based reprogramming and directed differentiation approaches ultimately exploit transcription factors to influence cellular identity. Here, we explore the evolution of reprogramming and directed differentiation approaches within the context of hepatocyte to β-cell transdifferentiation focussing on how the introduction of new techniques has improved our ability to generate β-cells.

Epigenetic control of hematopoiesis: the PU.1 chromatin connection

2014 ◽  
Vol 395 (11) ◽  
pp. 1265-1274 ◽  
Author(s):  
Boet van Riel ◽  
Frank Rosenbauer
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Current Knowledge ◽  
Dna Methyltransferases ◽  
Chromatin Remodelers ◽  
Cell Lineages ◽  
Protein Partners ◽  
Genome Wide

Abstract Purine-rich box1 (PU.1) is a transcription factor that not only has a key role in the development of most hematopoietic cell lineages but also in the suppression of leukemia. To exert these functions, PU.1 can cross-talk with multiple different proteins by forming complexes in order to activate or repress transcription. Among its protein partners are chromatin remodelers, DNA methyltransferases, and a number of other transcription factors with important roles in hematopoiesis. While a great deal of knowledge has been acquired about PU.1 function over the years, it was the development of novel genome-wide technologies, which boosted our understanding of how PU.1 acts on the chromatin to drive its repertoire of target genes. This review summarizes current knowledge and ideas of molecular mechanisms by which PU.1 controls hematopoiesis and suppresses leukemia.

scholarly journals Distinct Isoforms of the RFX Transcription Factor DAF-19 Regulate Ciliogenesis and Maintenance of Synaptic Activity

2008 ◽  
Vol 19 (12) ◽  
pp. 5517-5528 ◽  
Author(s):  
Gabriele Senti ◽  
Peter Swoboda
Keyword(s):  
Transcription Factor ◽  
Sensory Neurons ◽  
Neurodegenerative Disorders ◽  
Molecular Model ◽  
Synaptic Activity ◽  
Target Cells ◽  
C Elegans ◽  
Cellular Phenotypes ◽  
To Receive ◽  
Worm Caenorhabditis Elegans

Neurons form elaborate subcellular structures such as dendrites, axons, cilia, and synapses to receive signals from their environment and to transmit them to the respective target cells. In the worm Caenorhabditis elegans, lack of the RFX transcription factor DAF-19 leads to the absence of cilia normally found on 60 sensory neurons. We now describe and functionally characterize three different isoforms of DAF-19. The short isoform DAF-19C is specifically expressed in ciliated sensory neurons and sufficient to rescue all cilia-related phenotypes of daf-19 mutants. In contrast, the long isoforms DAF-19A/B function in basically all nonciliated neurons. We discovered behavioral and cellular phenotypes in daf-19 mutants that depend on the isoforms daf-19a/b. These novel synaptic maintenance phenotypes are reminiscent of synaptic decline seen in many human neurodegenerative disorders. The C. elegans daf-19 mutant worms can thus serve as a molecular model for the mechanisms of functional neuronal decline.

scholarly journals Landscape of allele-specific transcription factor binding in the human genome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sergey Abramov ◽  
Alexandr Boytsov ◽  
Daria Bykova ◽  
Dmitry D. Penzar ◽  
Ivan Yevshin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Specific Binding ◽  
Transcription Factor Binding ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Specific Transcription Factor ◽  
Factor Binding ◽  
Allele Specific

AbstractSequence variants in gene regulatory regions alter gene expression and contribute to phenotypes of individual cells and the whole organism, including disease susceptibility and progression. Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Differential transcription factor binding in heterozygous genomic loci provides a natural source of information on such regulatory variants. We present a novel approach to call the allele-specific transcription factor binding events at single-nucleotide variants in ChIP-Seq data, taking into account the joint contribution of aneuploidy and local copy number variation, that is estimated directly from variant calls. We have conducted a meta-analysis of more than 7 thousand ChIP-Seq experiments and assembled the database of allele-specific binding events listing more than half a million entries at nearly 270 thousand single-nucleotide polymorphisms for several hundred human transcription factors and cell types. These polymorphisms are enriched for associations with phenotypes of medical relevance and often overlap eQTLs, making candidates for causality by linking variants with molecular mechanisms. Specifically, there is a special class of switching sites, where different transcription factors preferably bind alternative alleles, thus revealing allele-specific rewiring of molecular circuitry.

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