scholarly journals Exploiting regulatory heterogeneity to systematically identify enhancers with high accuracy

2018 ◽  
Author(s):  
Hamutal Arbel ◽  
William W. Fisher ◽  
Ann S. Hammonds ◽  
Kenneth H. Wan ◽  
Soo Park ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Large Scale ◽  
Scale Validation ◽  
Expression Patterns ◽  
Prediction Method ◽  
High Accuracy ◽  
Enhancer Activity ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Scan

AbstractIdentifying functional enhancers elements in metazoan systems is a major challenge. For example, large-scale validation of enhancers predicted by ENCODE reveal false positive rates of at least 70%. Here we use the pregrastrula patterning network of Drosophila melanogaster to demonstrate that loss in accuracy in held out data results from heterogeneity of functional signatures in enhancer elements. We show that two classes of enhancer are active during early Drosophila embryogenesis and that by focusing on a single, relatively homogeneous class of elements, over 98% prediction accuracy can be achieved in a balanced, completely held-out test set. The class of well predicted elements is composed predominantly of enhancers driving multi-stage, segmentation patterns, which we designate segmentation driving enhancers (SDE). Prediction is driven by the DNA occupancy of early developmental transcription factors, with almost no additional power derived from histone modifications. We further show that improved accuracy is not a property of a particular prediction method: after conditioning on the SDE set, naïve Bayes and logistic regression perform as well as more sophisticated tools. Applying this method to a genome-wide scan, we predict 1,640 SDEs that cover 1.6% of the genome, 916 of which are novel. An analysis of 32 novel SDEs using wholemount embryonic imaging of stably integrated reporter constructs chosen throughout our prediction rank-list showed >90% drove expression patterns. We achieved 86.7% precision on a genome-wide scan, with an estimated recall of at least 98%, indicating high accuracy and completeness in annotating this class of functional elements.Significance StatementWe demonstrate a high accuracy method for predicting enhancers genome wide with > 85% precision as validated by transgenic reporter assays in Drosophila embryos. This is the first time such accuracy has been achieved in a metazoan system, allowing us to predict with high-confidence 1640 enhancers, 916 of which are novel. The predicted enhancers are demarcated by heterogeneous collections of epigenetic marks; many strong enhancers are free from classical indicators of activity, including H3K27ac, but are bound by key transcription factors. H3K27ac, often used as a one-dimensional predictor of enhancer activity, is an uninformative parameter in our data.

scholarly journals Exploiting regulatory heterogeneity to systematically identify enhancers with high accuracy

2018 ◽  
Vol 116 (3) ◽  
pp. 900-908 ◽  
Author(s):  
Hamutal Arbel ◽  
Sumanta Basu ◽  
William W. Fisher ◽  
Ann S. Hammonds ◽  
Kenneth H. Wan ◽  
...  
Keyword(s):  
Large Scale ◽  
Scale Validation ◽  
Expression Patterns ◽  
Prediction Method ◽  
High Accuracy ◽  
Genome Wide ◽  
Rank List ◽  
A Genome ◽  
Improved Accuracy ◽  
Genome Wide Scan

Identifying functional enhancer elements in metazoan systems is a major challenge. Large-scale validation of enhancers predicted by ENCODE reveal false-positive rates of at least 70%. We used the pregrastrula-patterning network of Drosophila melanogaster to demonstrate that loss in accuracy in held-out data results from heterogeneity of functional signatures in enhancer elements. We show that at least two classes of enhancers are active during early Drosophila embryogenesis and that by focusing on a single, relatively homogeneous class of elements, greater than 98% prediction accuracy can be achieved in a balanced, completely held-out test set. The class of well-predicted elements is composed predominantly of enhancers driving multistage segmentation patterns, which we designate segmentation driving enhancers (SDE). Prediction is driven by the DNA occupancy of early developmental transcription factors, with almost no additional power derived from histone modifications. We further show that improved accuracy is not a property of a particular prediction method: after conditioning on the SDE set, naïve Bayes and logistic regression perform as well as more sophisticated tools. Applying this method to a genome-wide scan, we predict 1,640 SDEs that cover 1.6% of the genome. An analysis of 32 SDEs using whole-mount embryonic imaging of stably integrated reporter constructs chosen throughout our prediction rank-list showed >90% drove expression patterns. We achieved 86.7% precision on a genome-wide scan, with an estimated recall of at least 98%, indicating high accuracy and completeness in annotating this class of functional elements.

scholarly journals Genome-wide investigation of the AP2/ERF gene family in  ginger: evolution and expression profiles during rhizome and inflorescence development

2021 ◽  
Author(s):  
Haitao Xing ◽  
Yusong Jiang ◽  
Xiaoling Long ◽  
Xiaoli Wu ◽  
Yun Ren ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Whole Genome Sequence ◽  
Chromosomal Distribution ◽  
Inflorescence Development ◽  
Systematic Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Erf Transcription Factors

Abstract Background:AP2/ERF transcription factors perform indispensable functions in various biological processes, such as plant growth, development, biotic and abiotic stresses responses. The AP2/ERF transcription factor family has been identified in many plants, and several AP2/ERF transcription factors from Arabidopsis (Arabidopsis thaliana) have been functionally characterized. However, little research has been conducted on the AP2/ERF genes of ginger (Zingiber officinale), which is an important edible and medicinal horticultural plant. The recently published whole genome sequence of ginger allowed us to study the tissue and expression profiles of AP2/ERF genes in ginger on a genome-wide basis.Results:In this study, 163 AP2/ERF genes of ginger (ZoAP2/ERF) were identified and renamed according to the chromosomal distribution of the ZoAP2/ERF genes. According to the number conserved domains and gene structure, the AP2/ERF genes were divided into three subfamilies by phylogenetic analysis, namely, AP2 (35 members), ERF (125 members) and RAV (3 members). A total of 10 motifs were detected in ginger AP2/ERF genes, and some of the unique motifs were found to be important for the function of ZoAP2/ERF genes.Conclusion:A comprehensive analysis of AP2/ERF gene expression patterns in different tissues and rhizome development stages by transcriptom sequence and quantitative real-time PCR (qRT-PCR) showed that they played an important role in the growth and development of ginger, and genes that might regulate rhizome and flower development were preliminarily identified. This systematic analysis establishes a foundation for further studies of the functional characteristics of ZoAP2/ERF genes and improvement of ginger.

scholarly journals Genome-Wide Identification, Characterization and Expression Analysis of TCP Transcription Factors in Petunia

2020 ◽  
Vol 21 (18) ◽  
pp. 6594
Author(s):  
Shuting Zhang ◽  
Qin Zhou ◽  
Feng Chen ◽  
Lan Wu ◽  
Baojun Liu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Plant Growth ◽  
Gene Family ◽  
Stress Responses ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Leaf Morphogenesis ◽  
Systematic Analysis ◽  
Genome Wide ◽  
A Genome

The plant-specific TCP transcription factors are well-characterized in both monocots and dicots, which have been implicated in multiple aspects of plant biological processes such as leaf morphogenesis and senescence, lateral branching, flower development and hormone crosstalk. However, no systematic analysis of the petunia TCP gene family has been described. In this work, a total of 66 petunia TCP genes (32 PaTCP genes in P. axillaris and 34 PiTCP genes in P. inflata) were identified. Subsequently, a systematic analysis of 32 PaTCP genes was performed. The phylogenetic analysis combined with structural analysis clearly distinguished the 32 PaTCP proteins into two classes—class Ι and class Ⅱ. Class Ⅱ was further divided into two subclades, namely, the CIN-TCP subclade and the CYC/TB1 subclade. Plenty of cis-acting elements responsible for plant growth and development, phytohormone and/or stress responses were identified in the promoter of PaTCPs. Distinct spatial expression patterns were determined among PaTCP genes, suggesting that these genes may have diverse regulatory roles in plant growth development. Furthermore, differential temporal expression patterns were observed between the large- and small-flowered petunia lines for most PaTCP genes, suggesting that these genes are likely to be related to petal development and/or petal size in petunia. The spatiotemporal expression profiles and promoter analysis of PaTCPs indicated that these genes play important roles in petunia diverse developmental processes that may work via multiple hormone pathways. Moreover, three PaTCP-YFP fusion proteins were detected in nuclei through subcellular localization analysis. This is the first comprehensive analysis of the petunia TCP gene family on a genome-wide scale, which provides the basis for further functional characterization of this gene family in petunia.

Genome-wide identification and expression profiling of the SPL family genes in wheat

Botany ◽  
2020 ◽  
Author(s):  
Fuye Guo ◽  
Qiuwei Lu ◽  
Jing Cang
Keyword(s):  
Transcription Factors ◽  
Gene Family ◽  
Expression Patterns ◽  
Vital Role ◽  
Functional Studies ◽  
Genome Wide ◽  
A Genome ◽  
Starting Point ◽  
Squamosa Promoter Binding Protein ◽  
Spl Gene

The SQUAMOSA promoter-binding protein-like (SPL) proteins constitute a family of plant-specific transcription factors that play a vital role in plant development. Wheat (Triticum aestivum, AABBDD) is universally well-known as a cash crop; however, the SPLs of this important crop have not been systematically investigated as yet. In the current study, we conducted a genome-wide survey in wheat and found 56 SPL genes belonging to 19 homologous groups. SPLs were divided into 7 classes by phylogenetic tree analyses. We mapped these genes on to the wheat chromosomes and examined their structures and conserved motifs. Moreover, we performed a synteny analysis on wheat, and summarized the SPL family as well as the evolutionary relationships between SPLs. Thereafter, we compared the expression patterns of wheat SPLs under different conditions, thereby confirming that SPLs play an important role in spike development. To conclude, the SPLs in triplets have analogous structures and similar expression patterns. The three-pair triplet response to jasmonic acid (JA) and abscisic acid (ABA) was determined by quantitative real-time polymerase chain reaction (RT-qPCR). This work provides a comprehensive understanding of the SPL gene family in wheat. Our investigation of the wheat SPL gene family provides a starting point for additional functional studies of these significant transcription factors in wheat.

scholarly journals Genome-Wide Analysis of Myeloblastosis-Related Genes in Brassica napus L. and Positive Modulation of Osmotic Tolerance by BnMRD107

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Li ◽  
Keyun Lin ◽  
Shuai Zhang ◽  
Jian Wu ◽  
Yujie Fang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Brassica Napus ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Functional Study ◽  
Evolutionary Analysis ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome

Myeloblastosis (MYB)-related transcription factors comprise a large subfamily of the MYB family. They play significant roles in plant development and in stress responses. However, MYB-related proteins have not been comprehensively investigated in rapeseed (Brassica napus L.). In the present study, a genome-wide analysis of MYB-related transcription factors was performed in rapeseed. We identified 251 Brassica napus MYB (BnMYB)-related members, which were divided phylogenetically into five clades. Evolutionary analysis suggested that whole genome duplication and segmental duplication events have played a significant role in the expansion of BnMYB-related gene family. Selective pressure of BnMYB-related genes was estimated using the Ka/Ks ratio, which indicated that BnMYB-related genes underwent strong purifying selection during evolution. In silico analysis showed that various development-associated, phytohormone-responsive, and stress-related cis-acting regulatory elements were enriched in the promoter regions of BnMYB-related genes. Furthermore, MYB-related genes with tissue or organ-specific, stress-responsive expression patterns were identified in B. napus based on temporospatial and abiotic stress expression profiles. Among the stress-responsive MYB-related genes, BnMRD107 was strongly induced by drought stress, and was therefore selected for functional study. Rapeseed seedlings overexpressing BnMRD107 showed improved resistance to osmotic stress. Our findings not only lay a foundation for further functional characterization of BnMYB-related genes, but also provide valuable clues to determine candidate genes for future genetic improvement of B. napus.

scholarly journals Genome-wide Ultrabithorax binding analysis reveals highly targeted genomic loci at developmental regulators and a potential connection to Polycomb-mediated regulation

2014 ◽  
Author(s):  
Daria Shlyueva ◽  
Antonio C.A. Meireles-Filho ◽  
Michaela Pagani ◽  
Alexander Stark
Keyword(s):  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Binding Sites ◽  
Polycomb Group ◽  
Thoracic Segment ◽  
Enhancer Activity ◽  
Animal Development ◽  
Genome Wide ◽  
A Genome

Hox homeodomain transcription factors are key regulators of animal development. They specify the identity of segments along the anterior-posterior body axis in metazoans by controlling the expression of diverse downstream targets, including transcription factors and signaling pathway components. The Drosophila melanogaster Hox factor Ultrabithorax (Ubx) directs the development of thoracic and abdominal segments and appendages, and loss of Ubx function can lead for example to the transformation of third thoracic segment appendages (e.g. halters) into second thoracic segment appendages (e.g. wings), resulting in a characteristic four-wing phenotype. Here we present a Drosophila melanogaster strain with a V5-epitope tagged Ubx allele, which we employed to obtain a high quality genome-wide map of Ubx binding sites using ChIP-seq. We confirm the sensitivity of the V5 ChIP-seq by recovering 7/8 of well-studied Ubx-dependent cis-regulatory regions. Moreover, we show that Ubx binding is predictive of enhancer activity as suggested by comparison with a genome-scale resource of in vivo tested enhancer candidates. We observed densely clustered Ubx binding sites at 12 extended genomic loci that included ANTP-C, BX-C, Polycomb complex genes, and other regulators and the clustered binding sites were frequently active enhancers. Furthermore, Ubx binding was detected at known Polycomb response elements (PREs) and was associated with significant enrichments of Pc and Pho ChIP signals in contrast to binding sites of other developmental TFs. Together, our results show that Ubx targets developmental regulators via strongly clustered binding sites and allow us to hypothesize that regulation by Ubx might involve Polycomb group proteins to maintain specific regulatory states in cooperative or mutually exclusive fashion, an attractive model that combines two groups of proteins with prominent gene regulatory roles during animal development.

scholarly journals Genome-wide identification and characterization of long non-coding RNAs involved in flag leaf senescence of rice

2021 ◽  
Author(s):  
Xiaoping Huang ◽  
Hongyu Zhang ◽  
Qiang Wang ◽  
Rong Guo ◽  
Lingxia Wei ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Leaf Senescence ◽  
Flag Leaf ◽  
Reduction Process ◽  
Sequencing Analysis ◽  
Biological Processes ◽  
Genome Wide ◽  
A Genome ◽  
Non Coding Rnas ◽  
Systematic Identification

Abstract Key message This study showed the systematic identification of long non-coding RNAs (lncRNAs) involving in flag leaf senescence of rice, providing the possible lncRNA-mRNA regulatory relationships and lncRNA-miRNA-mRNA ceRNA networks during leaf senescence. Abstract LncRNAs have been reported to play crucial roles in diverse biological processes. However, no systematic identification of lncRNAs associated with leaf senescence in plants has been studied. In this study, a genome-wide high throughput sequencing analysis was performed using rice flag leaves developing from normal to senescence. A total of 3953 lncRNAs and 38757 mRNAs were identified, of which 343 lncRNAs and 9412 mRNAs were differentially expressed. Through weighted gene co-expression network analysis (WGCNA), 22 continuously down-expressed lncRNAs targeting 812 co-expressed mRNAs and 48 continuously up-expressed lncRNAs targeting 1209 co-expressed mRNAs were considered to be significantly associated with flag leaf senescence. Gene Ontology results suggested that the senescence-associated lncRNAs targeted mRNAs involving in many biological processes, including transcription, hormone response, oxidation–reduction process and substance metabolism. Additionally, 43 senescence-associated lncRNAs were predicted to target 111 co-expressed transcription factors. Interestingly, 8 down-expressed lncRNAs and 29 up-expressed lncRNAs were found to separately target 12 and 20 well-studied senescence-associated genes (SAGs). Furthermore, analysis on the competing endogenous RNA (CeRNA) network revealed that 6 down-expressed lncRNAs possibly regulated 51 co-expressed mRNAs through 15 miRNAs, and 14 up-expressed lncRNAs possibly regulated 117 co-expressed mRNAs through 21 miRNAs. Importantly, by expression validation, a conserved miR164-NAC regulatory pathway was found to be possibly involved in leaf senescence, where lncRNA MSTRG.62092.1 may serve as a ceRNA binding with miR164a and miR164e to regulate three transcription factors. And two key lncRNAs MSTRG.31014.21 and MSTRG.31014.36 also could regulate the abscisic-acid biosynthetic gene BGIOSGA025169 (OsNCED4) and BGIOSGA016313 (NAC family) through osa-miR5809. The possible regulation networks of lncRNAs involving in leaf senescence were discussed, and several candidate lncRNAs were recommended for prior transgenic analysis. These findings will extend the understanding on the regulatory roles of lncRNAs in leaf senescence, and lay a foundation for functional research on candidate lncRNAs.

A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia

2006 ◽  
Vol 38 (7) ◽  
pp. 794-800 ◽  
Author(s):  
Anelia Horvath ◽  
Sosipatros Boikos ◽  
Christoforos Giatzakis ◽  
Audrey Robinson-White ◽  
Lionel Groussin ◽  
...  
Keyword(s):  
Gene Encoding ◽  
Genome Wide ◽  
A Genome ◽  
Adrenocortical Hyperplasia ◽  
Genome Wide Scan
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