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

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.

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TFmotifView: a webserver for the visualization of transcription factor motifs in genomic regions

Nucleic Acids Research ◽

10.1093/nar/gkaa252 ◽

2020 ◽

Vol 48 (W1) ◽

pp. W208-W217

Author(s):

Clémentine Leporcq ◽

Yannick Spill ◽

Delphine Balaramane ◽

Christophe Toussaint ◽

Michaël Weber ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcription Factors ◽

Regulation Of Gene Expression ◽

Genomic Region ◽

Regions Of Interest ◽

P Value ◽

Wide Range ◽

Genomic Regions ◽

Motif Information

Abstract Transcription factors (TFs) regulate the expression of gene expression. The binding specificities of many TFs have been deciphered and summarized as position-weight matrices, also called TF motifs. Despite the availability of hundreds of known TF motifs in databases, it remains non-trivial to quickly query and visualize the enrichment of known TF motifs in genomic regions of interest. Towards this goal, we developed TFmotifView, a web server that allows to study the distribution of known TF motifs in genomic regions. Based on input genomic regions and selected TF motifs, TFmotifView performs an overlap of the genomic regions with TF motif occurrences identified using a dynamic P-value threshold. TFmotifView generates three different outputs: (i) an enrichment table and scatterplot calculating the significance of TF motif occurrences in genomic regions compared to control regions, (ii) a genomic view of the organisation of TF motifs in each genomic region and (iii) a metaplot summarizing the position of TF motifs relative to the center of the regions. TFmotifView will contribute to the integration of TF motif information with a wide range of genomic datasets towards the goal to better understand the regulation of gene expression by transcription factors. TFmotifView is freely available at http://bardet.u-strasbg.fr/tfmotifview/.

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Long non-coding RNAs in brain tumors

NAR Cancer ◽

10.1093/narcan/zcaa041 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Keisuke Katsushima ◽

George Jallo ◽

Charles G Eberhart ◽

Ranjan J Perera

Keyword(s):

Gene Expression ◽

Brain Tumors ◽

Brain Cancer ◽

Regulation Of Gene Expression ◽

Therapeutic Targets ◽

Diagnostic Biomarkers ◽

Cancer Pathogenesis ◽

Current State ◽

Non Coding Rnas ◽

Post Transcriptional Regulation

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.

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The grapevine R2R3-type MYB transcription factor VdMYB1 positively regulates defense responses by activating the stilbene synthase gene 2 (VdSTS2)

BMC Plant Biology ◽

10.1186/s12870-019-1993-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Yihe Yu ◽

Dalong Guo ◽

Guirong Li ◽

Yingjun Yang ◽

Guohai Zhang ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcriptional Activation ◽

Molecular Mechanisms ◽

Plant Protection ◽

Defense Responses ◽

Stilbene Synthase ◽

Myb Transcription Factor ◽

Wide Range ◽

Grapevine Leaves

Abstract Background Resveratrol is a naturally occurring plant stilbene that exhibits a wide range of valuable biological and pharmacological properties. Although the beneficial effects of trans-resveratrol to human health and plant protection against fungal pathogens and abiotic stresses are well-established, yet little is known about the molecular mechanisms regulating stilbene biosynthesis in plant defense progress. Results Here, we cloned and identified the Chinese wild grape (Vitis davidii) R2R3-MYB transcription factor VdMYB1, which activates defense responses against invading pathogen. VdMYB1 transcripts were significantly upregulated after inoculation with the grapevine powdery mildew fungus Erysiphe necator (Schw.) Burr. Transient expression analysis using onion epidermal cells and Arabidopsis thaliana protoplasts showed that VdMYB1 was localized in the nucleus. Yeast one-hybrid assays revealed that VdMYB1 acts as a transcriptional activator. Grapevine leaves transiently overexpressing VdMYB1 showed a lower number of fungal conidiophores compared with wild-type leaves. Overexpression of VdMYB1 in grapevine leaves did not alter the expression of genes in salicylic acid- and jasmonate-dependent pathways, but affected the expression of stilbene synthase (STS) genes, key regulators of flavonoid metabolism. Results of electrophoretic mobility shift assays and in vivo transcriptional activation assays showed that VdMYB1 binds to the MYB binding site (MYBBS) in the STS2 gene promoter, thus activating STS2 transcription. In heterologous expression assays using tobacco leaves, VdMYB1 activated STS2 gene expression and increased the accumulation of resveratrol. Conclusions Our study showed that VdMYB1 activates STS2 gene expression to positively regulate defense responses, and increases the content of resveratrol in leaves.

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Expresso: A database and web server for exploring the interaction of transcription factors and their target genes in Arabidopsis thaliana using ChIP-Seq peak data

F1000Research ◽

10.12688/f1000research.10041.1 ◽

2017 ◽

Vol 6 ◽

pp. 372 ◽

Cited By ~ 7

Author(s):

Delasa Aghamirzaie ◽

Karthik Raja Velmurugan ◽

Shuchi Wu ◽

Doaa Altarawy ◽

Lenwood S. Heath ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcription Factors ◽

Chromatin Immunoprecipitation ◽

Target Genes ◽

Regulation Of Gene Expression ◽

Data Sets ◽

Motif Analysis ◽

Chromatin Immunoprecipitation Sequencing

Motivation: The increasing availability of chromatin immunoprecipitation sequencing (ChIP-Seq) data enables us to learn more about the action of transcription factors in the regulation of gene expression. Even though in vivo transcriptional regulation often involves the concerted action of more than one transcription factor, the format of each individual ChIP-Seq dataset usually represents the action of a single transcription factor. Therefore, a relational database in which available ChIP-Seq datasets are curated is essential. Results: We present Expresso (database and webserver) as a tool for the collection and integration of available Arabidopsis ChIP-Seq peak data, which in turn can be linked to a user’s gene expression data. Known target genes of transcription factors were identified by motif analysis of publicly available GEO ChIP-Seq data sets. Expresso currently provides three services: 1) Identification of target genes of a given transcription factor; 2) Identification of transcription factors that regulate a gene of interest; 3) Computation of correlation between the gene expression of transcription factors and their target genes. Availability: Expresso is freely available at http://bioinformatics.cs.vt.edu/expresso/

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Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000485395 ◽

2017 ◽

Vol 44 (3) ◽

pp. 948-966 ◽

Cited By ~ 28

Author(s):

Tesfaye Worku ◽

Dinesh Bhattarai ◽

Duncan Ayers ◽

Kai Wang ◽

Chen Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Gene Regulation ◽

Molecular Mechanisms ◽

Future Directions ◽

Diagnostic Biomarkers ◽

Functional Roles ◽

Gene Therapies ◽

Wide Range ◽

Recent Developments ◽

Non Coding Rnas

Long non-coding RNAs (lncRNAs), a class of non-coding transcripts, have recently been emerging with heterogeneous molecular actions, adding a new layer of complexity to gene-regulation networks in tumorigenesis. LncRNAs are considered important factors in several ovarian cancer histotypes, although few have been identified and characterized. Owing to their complexity and the lack of adapted molecular technology, the roles of most lncRNAs remain mysterious. Some lncRNAs have been reported to play functional roles in ovarian cancer and can be used as classifiers for personalized medicine. The intrinsic features of lncRNAs govern their various molecular mechanisms and provide a wide range of platforms to design different therapeutic strategies for treating cancer at a particular stage. Although we are only beginning to understand the functions of lncRNAs and their interactions with microRNAs (miRNAs) and proteins, the expanding literature indicates that lncRNA-miRNA interactions could be useful biomarkers and therapeutic targets for ovarian cancer. In this review, we discuss the genetic variants of lncRNAs, heterogeneous mechanisms of actions of lncRNAs in ovarian cancer tumorigenesis, and drug resistance. We also highlight the recent developments in using lncRNAs as potential prognostic and diagnostic biomarkers. Lastly, we discuss potential approaches for linking lncRNAs to future gene therapies, and highlight future directions in the field of ovarian cancer research.

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The role of epigenetic regulation in adaptive phenotypic plasticity of plants

Ukrainian Botanical Journal ◽

10.15407/ukrbotj78.05.347 ◽

2021 ◽

Vol 78 (5) ◽

pp. 347-359

Author(s):

E.L. Kordyum ◽

◽

D.V. Dubyna ◽

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Phenotypic Plasticity ◽

Epigenetic Regulation ◽

Molecular Mechanisms ◽

Regulation Of Gene Expression ◽

Model Species ◽

Wide Range ◽

Adaptive Phenotypic Plasticity

In recent decades, knowledge about the role of epigenetic regulation of gene expression in plant responses to external stimuli and in adaptation of plants to adverse environmental fluctuations have extended significantly. DNA methylation is considered as the main molecular mechanism that provides genomic information and contributes to the understanding of the molecular basis of phenotypic variations based on epigenetic modifications. Unfortunately, the vast majority of research in this area has been performed on the model species Arabidopsis thaliana. The development of the methylation-sensitive amplified polymorphism (MSAP) method has made it possible to implement the large-scale detection of DNA methylation alterations in wild non-model and agricultural plants with large and highly repetitive genomes in natural and manipulated habitats. The article presents current information on DNA methylation in species of natural communities and crops and its importance in plant development and adaptive phenotypic plasticity, along with brief reviews of current ideas about adaptive phenotypic plasticity and epigenetic regulation of gene expression. The great potential of further studies of the epigenetic role in phenotypic plasticity of a wide range of non-model species in natural populations and agrocenoses for understanding the molecular mechanisms of plant existence in the changing environment in onto- and phylogeny, directly related to the key tasks of forecasting the effects of global warming and crop selection, is emphasized. Specific taxa of the Ukrainian flora, which, in authors’ opinion, are promising and interesting for this type of research, are recommended.

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Quantitative models for accelerated protein dissociation from nucleosomal DNA

Nucleic Acids Research ◽

10.1093/nar/gku719 ◽

2014 ◽

Vol 42 (15) ◽

pp. 9753-9760 ◽

Cited By ~ 13

Author(s):

Cai Chen ◽

Ralf Bundschuh

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcription Factors ◽

Specific Binding ◽

Regulation Of Gene Expression ◽

Transcription Factor Binding ◽

General Mechanism ◽

Binding Model ◽

Factor Binding ◽

Protein Dissociation

Abstract Binding of transcription factors to their binding sites in promoter regions is the fundamental event in transcriptional gene regulation. When a transcription factor binding site is located within a nucleosome, the DNA has to partially unwrap from the nucleosome to allow transcription factor binding. This reduces the rate of transcription factor binding and is a known mechanism for regulation of gene expression via chromatin structure. Recently a second mechanism has been reported where transcription factor off-rates are dramatically increased when binding to target sites within the nucleosome. There are two possible explanations for such an increase in off-rate short of an active role of the nucleosome in pushing the transcription factor off the DNA: (i) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (ii) the nucleosome can change the equilibrium between specific and non-specific binding to the DNA. We explicitly model both scenarios and find that dimeric binding can explain a large increase in off-rate while the non-specific binding model cannot be reconciled with the large, experimentally observed increase. Our results suggest a general mechanism how nucleosomes increase transcription factor dissociation to promote exchange of transcription factors and regulate gene expression.

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Factors regulating lactoferrin gene expressionThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

Biochemistry and Cell Biology ◽

10.1139/o06-034 ◽

2006 ◽

Vol 84 (3) ◽

pp. 263-267 ◽

Cited By ~ 23

Author(s):

Christina T. Teng

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Transcription Factors ◽

Nuclear Receptors ◽

Transcriptional Activation ◽

Molecular Mechanisms ◽

Peer Review Process ◽

Regulation Of Gene Expression ◽

Limited Information ◽

Lactoferrin Gene

Regulation of gene expression by nuclear receptors and transcription factors involves the concerted action of multiple proteins. The process of transcriptional activation involves chromatin modification, nuclear receptor or transcription factor binding to the response element of the promoter, and coregulator recruitment. Despite advances in knowledge pertaining to the molecular mechanisms of gene regulation overall, there is very limited information available on the molecular mechanism of lactoferrin gene regulation. This review will outline novel information relating to general gene regulation and will discuss the current understanding of the regulation of lactoferrin gene expression by nuclear receptors and transcription factors.

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Unique Transcription Factor Functions Regulate Epigenetic and Transcriptional Dynamics During Cardiac Reprogramming

10.1101/642900 ◽

2019 ◽

Cited By ~ 1

Author(s):

Nicole R. Stone ◽

Casey A. Gifford ◽

Reuben Thomas ◽

Karishma J. B. Pratt ◽

Kaitlen Samse-Knapp ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcription Factors ◽

Molecular Mechanisms ◽

Ectopic Expression ◽

Chromatin Accessibility ◽

Transcriptional Dynamics ◽

Primary Driver ◽

Gene Expression Dynamics ◽

Direct Lineage Conversion

SUMMARYDirect lineage conversion, whereby a somatic cell assumes a new cellular identity, can be driven by ectopic expression of combinations of lineage-enriched transcription factors. To determine the molecular mechanisms by which expression of Gata4, Mef2c, and Tbx5 (GMT) induces direct reprogramming from a cardiac fibroblast toward an induced cardiomyocyte, we performed a comprehensive transcriptomic and epigenomic interrogation of the reprogramming process. Single cell RNA sequencing indicated that a reprogramming trajectory was acquired within 48 hours of GMT introduction, did not require cell division, and was limited mainly by successful expression of GMT. Evaluation of chromatin accessibility by ATAC-seq supported the expression dynamics and revealed widespread chromatin remodeling at early stages of the reprogramming process. Chromatin immunoprecipitation followed by sequencing of each factor alone or in combinations revealed that GMT bind DNA individually and in combination, and that ectopic expression of either Mef2c or Tbx5 is sufficient in some contexts to increase accessibility. We also find evidence for cooperative facilitation and refinement of each factor’s binding in a combinatorial setting. A random-forest classifier that integrated the observed gene expression dynamics with regions of dynamic chromatin accessibility suggested Tbx5 binding is a primary driver of gene expression changes and revealed additional transcription factor motifs co-segregating with reprogramming factor motifs, suggesting new factors that may be involved in the reprogramming process. These results begin to explain the mechanisms by which transcription factors normally expressed in multiple germ layers can function combinatorially to direct lineage conversion.

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Regulation of gene expression in the nervous system

Biochemical Journal ◽

10.1042/bj20080963 ◽

2008 ◽

Vol 414 (3) ◽

pp. 327-341 ◽

Cited By ~ 42

Author(s):

Lezanne Ooi ◽

Ian C. Wood

Keyword(s):

Gene Expression ◽

Nervous System ◽

Transcription Factors ◽

Gene Regulatory Networks ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Cell Types ◽

Gene Regulatory

The nervous system contains a multitude of cell types which are specified during development by cascades of transcription factors acting combinatorially. Some of these transcription factors are only active during development, whereas others continue to function in the mature nervous system to maintain appropriate gene-expression patterns in differentiated cells. Underpinning the function of the nervous system is its plasticity in response to external stimuli, and many transcription factors are involved in regulating gene expression in response to neuronal activity, allowing us to learn, remember and make complex decisions. Here we review some of the recent findings that have uncovered the molecular mechanisms that underpin the control of gene regulatory networks within the nervous system. We highlight some recent insights into the gene-regulatory circuits in the development and differentiation of cells within the nervous system and discuss some of the mechanisms by which synaptic transmission influences transcription-factor activity in the mature nervous system. Mutations in genes that are important in epigenetic regulation (by influencing DNA methylation and post-translational histone modifications) have long been associated with neuronal disorders in humans such as Rett syndrome, Huntington's disease and some forms of mental retardation, and recent work has focused on unravelling their mechanisms of action. Finally, the discovery of microRNAs has produced a paradigm shift in gene expression, and we provide some examples and discuss the contribution of microRNAs to maintaining dynamic gene regulatory networks in the brain.

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