Genome-wide Search for Zelda-like Chromatin Signatures Identifies GAF as a Pioneer Factor in Early Fly Development

Mapping Intimacies ◽

10.1101/104067 ◽

2017 ◽

Author(s):

Arbel Moshe ◽

Tommy Kaplan

Keyword(s):

Transcriptional Activation ◽

Computational Method ◽

Gaga Factor ◽

Genome Wide ◽

A Genome ◽

Genome Wide Search ◽

Pioneer Factor ◽

Pioneer Factors ◽

Early Developmental ◽

Chromatin Patterns

The protein Zelda was shown to play a key role in early Drosophila development, binding thousands of promoters and enhancers prior to maternal-to-zygotic transition (MZT), and marking them for transcriptional activation. Recently, we showed that Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters. Intriguingly, some Zelda sites still maintain these chromatin patterns in Drosophila embryos lacking maternal Zelda protein. This suggests that additional Zelda-like pioneer factors may act in early fly embryos. We developed a computational method to analyze and refine the chromatin landscape surrounding early Zelda peaks, using a multi-channel spectral clustering. This allowed us to characterize their chromatin patterns through MZT (mitotic cycles 8-14). Specifically, we focused on H3K4me1, H3K4me3, H3K18ac, H3K27ac, and H3K27me3 and identified three different classes of chromatin signatures, matching "promoters", "enhancers" and "transiently bound" Zelda peaks. We then further scanned the genome using these chromatin patterns and identified additional loci - with no Zelda binding - that show similar chromatin patterns, resulting with hundreds of Zelda- independent putative enhancers. These regions were found to be enriched with GAGA factor (GAF, Trl), and are typically located near early developmental zygotic genes. Overall our analysis suggests that GAF, together with Zelda, plays an important role in activating the zygotic genome. As we show, our computational approach offers an efficient algorithm for characterizing chromatin signatures around some loci of interest, and allows a genome-wide identification of additional loci with similar chromatin patterns.

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Identification and Analysis of the AP2 Subfamily Transcription Factors in the Pecan (Carya illinoinensis)

International Journal of Molecular Sciences ◽

10.3390/ijms222413568 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13568

Author(s):

Zhengfu Yang ◽

Hongmiao Jin ◽

Junhao Chen ◽

Caiyun Li ◽

Jiani Wang ◽

...

Keyword(s):

Transcriptional Activation ◽

Expression Patterns ◽

Carya Illinoinensis ◽

Expression Levels ◽

Cis Acting ◽

Similar Expression ◽

Genome Wide ◽

A Genome ◽

Genome Wide Search ◽

Ethylene Responsive Factor

The AP2 transcriptional factors (TFs) belong to the APETALA2/ ethylene-responsive factor (AP2/ERF) superfamily and regulate various biological processes of plant growth and development, as well as response to biotic and abiotic stresses. However, genome-wide research on the AP2 subfamily TFs in the pecan (Carya illinoinensis) is rarely reported. In this paper, we identify 30 AP2 subfamily genes from pecans through a genome-wide search, and they were unevenly distributed on the pecan chromosomes. Then, a phylogenetic tree, gene structure and conserved motifs were further analyzed. The 30 AP2 genes were divided into euAP2, euANT and basalANT three clades. Moreover, the cis-acting elements analysis showed many light responsive elements, plant hormone-responsive elements and abiotic stress responsive elements are found in CiAP2 promoters. Furthermore, a qPCR analysis showed that genes clustered together usually shared similar expression patterns in euAP2 and basalANT clades, while the expression pattern in the euANT clade varied greatly. In developing pecan fruits, CiAP2-5, CiANT1 and CiANT2 shared similar expression patterns, and their expression levels decreased with fruit development. CiANT5 displayed the highest expression levels in developing fruits. The subcellular localization and transcriptional activation activity assay demonstrated that CiANT5 is located in the nucleus and functions as a transcription factor with transcriptional activation activity. These results help to comprehensively understand the pecan AP2 subfamily TFs and lay the foundation for further functional research on pecan AP2 family genes.

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Epigenome-Wide Study Identified Methylation Sites Associated with the Risk of Obesity

Nutrients ◽

10.3390/nu13061984 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1984

Author(s):

Majid Nikpay ◽

Sepehr Ravati ◽

Robert Dent ◽

Ruth McPherson

Keyword(s):

Quantitative Trait Locus ◽

Quantitative Trait ◽

Rare Variants ◽

Genome Wide ◽

A Genome ◽

Genome Wide Search ◽

Risk Snps ◽

Trait Locus ◽

Genomic Regions ◽

Eqtl Data

Here, we performed a genome-wide search for methylation sites that contribute to the risk of obesity. We integrated methylation quantitative trait locus (mQTL) data with BMI GWAS information through a SNP-based multiomics approach to identify genomic regions where mQTLs for a methylation site co-localize with obesity risk SNPs. We then tested whether the identified site contributed to BMI through Mendelian randomization. We identified multiple methylation sites causally contributing to the risk of obesity. We validated these findings through a replication stage. By integrating expression quantitative trait locus (eQTL) data, we noted that lower methylation at cg21178254 site upstream of CCNL1 contributes to obesity by increasing the expression of this gene. Higher methylation at cg02814054 increases the risk of obesity by lowering the expression of MAST3, whereas lower methylation at cg06028605 contributes to obesity by decreasing the expression of SLC5A11. Finally, we noted that rare variants within 2p23.3 impact obesity by making the cg01884057 site more susceptible to methylation, which consequently lowers the expression of POMC, ADCY3 and DNAJC27. In this study, we identify methylation sites associated with the risk of obesity and reveal the mechanism whereby a number of these sites exert their effects. This study provides a framework to perform an omics-wide association study for a phenotype and to understand the mechanism whereby a rare variant causes a disease.

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A Genome-Wide Search For Susceptibility Loci to Human Essential Hypertension

Hypertension ◽

10.1161/01.hyp.35.6.1291 ◽

2000 ◽

Vol 35 (6) ◽

pp. 1291-1296 ◽

Cited By ~ 40

Author(s):

Pankaj Sharma ◽

Jennie Fatibene ◽

Franco Ferraro ◽

Haiyan Jia ◽

Sue Monteith ◽

...

Keyword(s):

Essential Hypertension ◽

Susceptibility Loci ◽

Genome Wide ◽

A Genome ◽

Genome Wide Search

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Low temperature triggers genome-wide hypermethylation of transposable elements and centromeres in maize

10.1101/573915 ◽

2019 ◽

Cited By ~ 1

Author(s):

Zeineb Achour ◽

Johann Joets ◽

Martine Leguilloux ◽

Hélène Sellier ◽

Jean-Philippe Pichon ◽

...

Keyword(s):

Dna Methylation ◽

Transposable Elements ◽

Transcriptional Activation ◽

Gene Expression Regulation ◽

Environmental Cues ◽

Specific Response ◽

Genome Wide ◽

A Genome ◽

Response To Stress ◽

Context Specific

ABSTRACTCharacterizing the molecular processes developed by plants to respond to environmental cues is a major task to better understand local adaptation. DNA methylation is a chromatin mark involved in the transcriptional silencing of transposable elements (TEs) and gene expression regulation. While the molecular bases of DNA methylation regulation are now well described, involvement of DNA methylation in plant response to environmental cues remains poorly characterized. Here, using the TE-rich maize genome and analyzing methylome response to prolonged cold at the chromosome and feature scales, we investigate how genomic architecture affects methylome response to stress in a cold-sensitive genotype. Interestingly, we show that cold stress induces a genome-wide methylation increase through the hypermethylation of TE sequences and centromeres. Our work highlights a cytosine context-specific response of TE methylation that depends on TE types, chromosomal location and proximity to genes. The patterns observed can be explained by the parallel transcriptional activation of multiple DNA methylation pathways that methylate TEs in the various chromatin locations where they reside. Our results open new insights into the possible role of genome-wide DNA methylation in phenotypic response to stress.

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Genome-Wide Prediction of Coaxial Helical Stacking Using Random Forests and Covariance Models

International Journal of Artificial Intelligence Tools ◽

10.1142/s0218213014600082 ◽

2014 ◽

Vol 23 (03) ◽

pp. 1460008

Author(s):

Kevin Byron ◽

Jason T. L. Wang ◽

Dongrong Wen

Keyword(s):

Random Forests ◽

Life Science ◽

Science Research ◽

Genomic Region ◽

Computational Approach ◽

Search Method ◽

Genome Wide ◽

A Genome ◽

Genome Wide Search ◽

Covariance Models

Developing effective artificial intelligence tools to find motifs in DNA, RNA and proteins poses a challenging yet important problem in life science research. In this paper, we present a computational approach for finding RNA tertiary motifs in genomic sequences. Specifically, we predict genomic coordinate locations for coaxial helical stackings in 3-way RNA junctions. These predictions are provided by our tertiary motif search package, named CSminer, which utilizes two versatile methodologies: random forests and covariance models. A coaxial helical stacking tertiary motif occurs in a 3-way RNA junction where two separate helical elements form a pseudocontiguous helix and provide thermodynamic stability to the RNA molecule as a whole. Our CSminer tool first uses a genome-wide search method based on covariance models to find a genomic region that may potentially contain a coaxial helical stacking tertiary motif. CSminer then uses a random forests classifier to predict whether the genomic region indeed contains the tertiary motif. Experimental results demonstrate the effectiveness of our approach.

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Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5

Blood ◽

10.1182/blood-2007-07-104133 ◽

2008 ◽

Vol 111 (3) ◽

pp. 1217-1226 ◽

Cited By ~ 317

Author(s):

Yun Chen ◽

David H. Gorski

Keyword(s):

Binding Sites ◽

Untranslated Region ◽

Vascular Endothelial Cells ◽

Homeobox Gene ◽

Vascular Endothelial ◽

Down Regulation ◽

Antiangiogenic Activity ◽

Genome Wide ◽

A Genome ◽

Genome Wide Search

Abstract Angiogenesis is critical to tumor progression. The homeobox gene GAX inhibits angiogenesis in vascular endothelial cells (ECs). We have identified a microRNA (miR-130a) that regulates GAX expression and hypothesized that it plays a major role in modulating GAX activity in ECs. A 280-bp fragment from the GAX 3′-untranslated region (3′-UTR) containing 2 miR-130a targeting sites was observed to be required for the rapid down-regulation of GAX expression by serum and proangiogenic factors, whereas the activity of the GAX promoter did not vary with exposure to serum or proangiogenic factors. This same 280-bp sequence in the GAX 3′-UTR cloned into the psiCHECK2-Luciferase vector mediated serum-induced down-regulation of the reporter gene when placed 3′ of it. Finally, forced expression of miR-130a inhibits GAX expression through this specific GAX 3′-UTR sequence. A genome-wide search for other possible miR-130a binding sites revealed an miR-130a targeting site in the 3′-UTR of the antiangiogenic homeobox gene HOXA5, the expression and antiangiogenic activity of which are also inhibited by miR-130a. From these data, we conclude that miR-130a is a regulator of the angiogenic phenotype of vascular ECs largely through its ability to modulate the expression of GAX and HOXA5.

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