scholarly journals TFregulomeR reveals transcription factors’ context-specific features and functions

2019 ◽  
Vol 48 (2) ◽  
pp. e10-e10 ◽  
Author(s):  
Quy Xiao Xuan Lin ◽  
Denis Thieffry ◽  
Sudhakar Jha ◽  
Touati Benoukraf
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Leucine Zipper ◽  
Cell Types ◽  
Fine Tuning ◽  
A Cell ◽  
Context Specific ◽  
Gene Ontologies ◽  
Different Cell Types

Abstract Transcription factors (TFs) are sequence-specific DNA binding proteins, fine-tuning spatiotemporal gene expression. Since genomic occupancy of a TF is highly dynamic, it is crucial to study TF binding sites (TFBSs) in a cell-specific context. To date, thousands of ChIP-seq datasets have portrayed the genomic binding landscapes of numerous TFs in different cell types. Although these datasets can be browsed via several platforms, tools that can operate on that data flow are still lacking. Here, we introduce TFregulomeR (https://github.com/benoukraflab/TFregulomeR), an R-library linked to an up-to-date compendium of cistrome and methylome datasets, implemented with functionalities that facilitate integrative analyses. In particular, TFregulomeR enables the characterization of TF binding partners and cell-specific TFBSs, along with the study of TF’s functions in the context of different partnerships and DNA methylation levels. We demonstrated that TFs’ target gene ontologies can differ notably depending on their partners and, by re-analyzing well characterized TFs, we brought to light that numerous leucine zipper TFBSs derived from ChIP-seq experiments documented in current databases were inadequately characterized, due to the fact that their position weight matrices were assembled using a mixture of homodimer and heterodimer binding sites. Altogether, analyses of context-specific transcription regulation with TFregulomeR foster our understanding of regulatory network-dependent TF functions.

scholarly journals Large-scale multi-omics analysis suggests specific roles for intragenic cohesin in transcriptional regulation

2021 ◽  
Author(s):  
Jiankang Wang ◽  
Masashige Bando ◽  
Katsuhiko Shirahige ◽  
Ryuichiro Nakato
Keyword(s):  
Transcriptional Regulation ◽  
Rna Polymerase Ii ◽  
Binding Sites ◽  
Large Scale ◽  
Gene Activation ◽  
Cell Types ◽  
Chromatin Interaction ◽  
Context Specific ◽  
Comprehensive Characterization

Cohesin, an essential protein complex for chromosome segregation, regulates transcription through a variety of mechanisms. It is not a trivial task to genome-widely assign the diverse cohesin functions. Moreover, the context-specific roles of cohesin-mediated interactions, especially on intragenic regions, have not been thoroughly investigated. Here we performed a comprehensive characterization of cohesin binding sites in several human cell types. We integrated epigenomic, transcriptomic and chromatin interaction data with and without transcriptional stimulation, to explore context-specific functions of intragenic cohesin related to gene activation. We identified a new subset of cohesin binding sites, decreased intragenic cohesin sites (DICs), which have a different function from previously known ones. The intron-enriched DICs were negatively correlated with transcriptional regulation: a subgroup of DICs were related to enhancer markers and paused RNA polymerase II, whereas others contributed to chromatin architecture. We implemented machine learning and successfully isolated DICs with distinct genomic features. We observed DICs in various cell types, including cells from cohesinopathy patients. These results suggest a previously unidentified function of cohesin at intragenic regions for transcription regulation.

scholarly journals MiR-7 in Cancer Development

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 325
Author(s):  
Petra Korać ◽  
Mariastefania Antica ◽  
Maja Matulić
Keyword(s):  
Cell Fate ◽  
Dominant Role ◽  
Tumor Development ◽  
Mrna Translation ◽  
Cell Types ◽  
Fine Tuning ◽  
Non Coding Rna ◽  
Tumor Types ◽  
Different Cell Types ◽  
The Brain

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

scholarly journals Cloning and functional characterization of the human fractalkine receptor promoter regions

2002 ◽  
Vol 368 (3) ◽  
pp. 753-760 ◽  
Author(s):  
Alexandre GARIN ◽  
Philippe PELLET ◽  
Philippe DETERRE ◽  
Patrice DEBRÉ ◽  
Christophe COMBADIÈRE
Keyword(s):  
Functional Characterization ◽  
Cell Types ◽  
Promoter Regions ◽  
Exon 2 ◽  
Reading Frame ◽  
Fractalkine Receptor ◽  
A Cell ◽  
Exon 4 ◽  
Coronary Events

We have previously shown that reduced expression of the fractalkine receptor, CX3CR1, is correlated with rapid HIV disease progression and with reduced susceptibility to acute coronary events. In order to elucidate the mechanisms underlying transcriptional regulation of CX3CR1 expression, we structurally and functionally characterized the CX3CR1 gene. It consists of four exons and three introns spanning over 18kb. Three transcripts are produced by splicing the three untranslated exons with exon 4, which contains the complete open reading frame. The transcript predominantly found in leucocytes corresponds to the splicing of exon 2 with exon 4. Transcripts corresponding to splicing of exons 1 and 4 are less abundant in leucocytes and splicing of exons 3 and 4 are rare longer transcripts. A constitutive promoter activity was found in the regions extending upstream from untranslated exons 1 and 2. Interestingly, exons 1 and 2 enhanced the activity of their respective promoters in a cell-specific manner. These data show that the CX3CR1 gene is controlled by three distinct promoter regions, which are regulated by their respective untranslated exons and that lead to the transcription of three mature messengers. This highly complex regulation may allow versatile and precise expression of CX3CR1 in various cell types.

scholarly journals HOT or not: examining the basis of high-occupancy target regions

2017 ◽  
Author(s):  
Katarzyna Wreczycka ◽  
Vedran Franke ◽  
Bora Uyar ◽  
Ricardo Wurmus ◽  
Altuna Akalin
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Cell Types ◽  
Data Sets ◽  
Gene Promoters ◽  
Quadruplex Dna ◽  
Golden Standard ◽  
Multiple Cell ◽  
Multiple Species

AbstractHigh-occupancy target (HOT) regions are the segments of the genome with unusually high number of transcription factor binding sites. These regions are observed in multiple species and thought to have biological importance due to high transcription factor occupancy. Furthermore, they coincide with house-keeping gene promoters and the associated genes are stably expressed across multiple cell types. Despite these features, HOT regions are solemnly defined using ChIP-seq experiments and shown to lack canonical motifs for transcription factors that are thought to be bound there. Although, ChIP-seq experiments are the golden standard for finding genome-wide binding sites of a protein, they are not noise free. Here, we show that HOT regions are likely to be ChIP-seq artifacts and they are similar to previously proposed “hyper-ChIPable” regions. Using ChIP-seq data sets for knocked-out transcription factors, we demonstrate presence of false positive signals on HOT regions. We observe sequence characteristics and genomic features that are discriminatory of HOT regions, such as GC/CpG-rich k-mers and enrichment of RNA-DNA hybrids (R-loops) and DNA tertiary structures (G-quadruplex DNA). The artificial ChIP-seq enrichment on HOT regions could be associated to these discriminatory features. Furthermore, we propose strategies to deal with such artifacts for the future ChIP-seq studies.

scholarly journals Virtual ChIP-seq: predicting transcription factor binding by learning from the transcriptome

2018 ◽  
Author(s):  
Mehran Karimzadeh ◽  
Michael M. Hoffman
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Cell Types ◽  
Transcription Factor Binding ◽  
Regulatory Function ◽  
Factor Binding ◽  
Link Type ◽  
Genomic Regions ◽  
Factor Sequence

AbstractMotivationIdentifying transcription factor binding sites is the first step in pinpointing non-coding mutations that disrupt the regulatory function of transcription factors and promote disease. ChIP-seq is the most common method for identifying binding sites, but performing it on patient samples is hampered by the amount of available biological material and the cost of the experiment. Existing methods for computational prediction of regulatory elements primarily predict binding in genomic regions with sequence similarity to known transcription factor sequence preferences. This has limited efficacy since most binding sites do not resemble known transcription factor sequence motifs, and many transcription factors are not even sequence-specific.ResultsWe developed Virtual ChIP-seq, which predicts binding of individual transcription factors in new cell types using an artificial neural network that integrates ChIP-seq results from other cell types and chromatin accessibility data in the new cell type. Virtual ChIP-seq also uses learned associations between gene expression and transcription factor binding at specific genomic regions. This approach outperforms methods that predict TF binding solely based on sequence preference, pre-dicting binding for 36 transcription factors (Matthews correlation coefficient > 0.3).AvailabilityThe datasets we used for training and validation are available at https://virchip.hoffmanlab.org. We have deposited in Zenodo the current version of our software (http://doi.org/10.5281/zenodo.1066928), datasets (http://doi.org/10.5281/zenodo.823297), predictions for 36 transcription factors on Roadmap Epigenomics cell types (http://doi.org/10.5281/zenodo.1455759), and predictions in Cistrome as well as ENCODE-DREAM in vivo TF Binding Site Prediction Challenge (http://doi.org/10.5281/zenodo.1209308).

scholarly journals The histone variant H2A.Z and chromatin remodeler BRAHMA act coordinately and antagonistically to regulate transcription and nucleosome dynamics in Arabidopsis

2018 ◽  
Author(s):  
E. Shannon Torres ◽  
Roger B. Deal
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Binding Sites ◽  
Transcriptional Repression ◽  
Nucleosome Positioning ◽  
Chromatin Organization ◽  
Histone H2a ◽  
Nucleosome Dynamics ◽  
Environmentally Responsive ◽  
Context Specific

ABSTRACTPlants adapt to changes in their environment by regulating transcription and chromatin organization. The histone H2A variant H2A.Z and the SWI2/SNF2 ATPase BRAHMA have overlapping roles in positively and negatively regulating environmentally responsive genes in Arabidopsis, but the extent of this overlap was uncharacterized. Both have been associated with various changes in nucleosome positioning and stability in different contexts, but their specific roles in transcriptional regulation and chromatin organization need further characterization. We show that H2A.Z and BRM act both cooperatively and antagonistically to contribute directly to transcriptional repression and activation of genes involved in development and response to environmental stimuli. We identified 8 classes of genes that show distinct relationships between H2A.Z and BRM and their roles in transcription. We found that H2A.Z contributes to a range of different nucleosome properties, while BRM stabilizes nucleosomes where it binds and destabilizes and/or repositions flanking nucleosomes. H2A.Z and BRM contribute to +1 nucleosome destabilization, especially where they coordinately regulate transcription. We also found that at genes regulated by both BRM and H2A.Z, both factors overlap with the binding sites of light-regulated transcription factors PIF4, PIF5, and FRS9, and that some of the FRS9 binding sites are dependent on H2A.Z and BRM for accessibility. Collectively, we comprehensively characterized the antagonistic and cooperative contributions of H2A.Z and BRM to transcriptional regulation, and illuminated their interrelated roles in chromatin organization. The variability observed in their individual functions implies that both BRM and H2A.Z have more context-specific roles within diverse chromatin environments than previously assumed.

The underground life of homeodomain-leucine zipper transcription factors

2021 ◽  
Author(s):  
Perotti M F ◽  
Arce A L ◽  
R L Chan
Keyword(s):  
Transcription Factors ◽  
Root Development ◽  
Leucine Zipper ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Large Family ◽  
Cell Types ◽  
Structural Features ◽  
Specific Cell ◽  
High Plasticity

Abstract Roots are the anchorage organs of plants, responsible for water and nutrient uptake, exhibiting high plasticity. Root architecture is driven by the interactions of biomolecules, including transcription factors (TFs) and hormones that are crucial players regulating root plasticity. Multiple TF families are involved in root development; some, such as ARFs and LBDs, have been well characterized, whereas others remain less investigated. In this review, we synthesize the current knowledge about the involvement of the large family of homeodomain-leucine zipper (HD-Zip) TFs in root development. This family is divided into four subfamilies (I to IV), mainly according to structural features, such as additional motifs aside from HD-Zip, as well as their size, gene structure, and expression patterns. We explored and analyzed public databases and the scientific literature regarding HD-Zip TFs in Arabidopsis and other species. Most members of the four HD-Zip subfamilies are expressed in specific cell types and several ones from each group have assigned functions in root development. Notably, a high proportion of the studied proteins are part of intricate regulation pathways involved in primary and lateral root growth and development.

Implications of microRNAs in the pathogenesis of atherosclerosis and prospects for therapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Armita Mahdavi Gorabi ◽  
Mohsen Ghanbari ◽  
Thozhukat Sathyapalan ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Immune Cell ◽  
Cholesterol Metabolism ◽  
Current Knowledge ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Fine Tuning ◽  
Lipid Uptake ◽  
Atherosclerosis Development ◽  
Signaling Receptors ◽  
Different Cell Types

MicroRNAs (miRNAs) are non-coding RNAs containing around 22 nucleotides, which are expressed in vertebrates and plants. They act as posttranscriptional gene expression regulators, fine-tuning various biological processes in different cell types. There is emerging evidence on their role in different stages of atherosclerosis. In addition to regulating the inflammatory cells involved in atherosclerosis, miRNAs play fundamental roles in the pathophysiology of atherosclerosis such as endothelial cell (EC) dysfunction, the aberrant function of the vascular smooth muscle cell (VSMC) and cholesterol metabolism. Moreover, miRNAs participate in several pathogenic pathways of atherosclerotic plaque development, including their effects on immune cell signaling receptors and lipid uptake. In this study, we review our current knowledge of the regulatory role of miRNAs in various pathogenic pathways underlying atherosclerosis development and also outline potential clinical applications of miRNAs in atherosclerosis.

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