scholarly journals CharPlant: A De Novo Open Chromatin Region Prediction Tool for Plant Genomes

Author(s):  
Yin Shen ◽  
Ling-Ling Chen ◽  
Junxiang Gao
2020 ◽  
Author(s):  
Yin Shen ◽  
Ling-Ling Chen ◽  
Junxiang Gao

AbstractChromatin accessibility is a highly informative structural feature for understanding gene transcription regulation because it indicates the degree to which nuclear macromolecules such as proteins and RNA can access chromosomal DNA. Studies show that chromatin accessibility is highly dynamic during stress response, stimulus response, and developmental transition. Moreover, physical access to chromosomal DNA in eukaryotes is highly cell-specific. Therefore, current technologies such as DNase-seq, ATAC-seq, and FAIRE-seq reveal only a portion of the open chromatin regions (OCRs) present in a given species. Thus, the genome-wide distribution of OCRs remains unknown. In this study, we developed a bioinformatics tool called CharPlant for the de novo prediction of chromatin accessible regions in plant genomes. To develop this tool, we constructed a three-layer convolutional neural network (CNN) and subsequently trained the CNN using DNase-seq and ATAC-seq datasets of four plant species. The model simultaneously learns the sequence motifs and regulatory logics, which are jointly used to determine DNA accessibility. All of these steps are integrated into CharPlant, which can be run using a simple command line. The results of data analysis using CharPlant in this study demonstrate its prediction power and computational efficiency. To our knowledge, CharPlant is the first de novo prediction tool that can identify potential OCRs in the whole genome. The source code of CharPlant and supporting files are freely downloadable from https://github.com/Yin-Shen/CharPlant.


2020 ◽  
Vol 37 (12) ◽  
pp. 3576-3600
Author(s):  
Di Chen ◽  
Marzia A Cremona ◽  
Zongtai Qi ◽  
Robi D Mitra ◽  
Francesca Chiaromonte ◽  
...  

Abstract Long INterspersed Elements-1 (L1s) constitute >17% of the human genome and still actively transpose in it. Characterizing L1 transposition across the genome is critical for understanding genome evolution and somatic mutations. However, to date, L1 insertion and fixation patterns have not been studied comprehensively. To fill this gap, we investigated three genome-wide data sets of L1s that integrated at different evolutionary times: 17,037 de novo L1s (from an L1 insertion cell-line experiment conducted in-house), and 1,212 polymorphic and 1,205 human-specific L1s (from public databases). We characterized 49 genomic features—proxying chromatin accessibility, transcriptional activity, replication, recombination, etc.—in the ±50 kb flanks of these elements. These features were contrasted between the three L1 data sets and L1-free regions using state-of-the-art Functional Data Analysis statistical methods, which treat high-resolution data as mathematical functions. Our results indicate that de novo, polymorphic, and human-specific L1s are surrounded by different genomic features acting at specific locations and scales. This led to an integrative model of L1 transposition, according to which L1s preferentially integrate into open-chromatin regions enriched in non-B DNA motifs, whereas they are fixed in regions largely free of purifying selection—depleted of genes and noncoding most conserved elements. Intriguingly, our results suggest that L1 insertions modify local genomic landscape by extending CpG methylation and increasing mononucleotide microsatellite density. Altogether, our findings substantially facilitate understanding of L1 integration and fixation preferences, pave the way for uncovering their role in aging and cancer, and inform their use as mutagenesis tools in genetic studies.


2006 ◽  
Vol 26 (17) ◽  
pp. 6357-6371 ◽  
Author(s):  
Chunhong Yan ◽  
Douglas D. Boyd

ABSTRACT Histone modifications are associated with distinct transcription states and serve as heritable epigenetic markers for chromatin structure and function. While H3 K9 methylation defines condensed heterochromatin that is able to silence a nearby gene, how gene silencing within euchromatin regions is achieved remains elusive. We report here that histone H3 K4 methylation or K9/K14 acetylation defines distinct chromatin regions permissive or nonpermissive for transgene expression. A permissive chromatin region is enriched in H3 K4 methylation and H3 acetylation, while a nonpermissive region is poor in or depleted of these two histone modifications. The histone modification states of the permissive chromatin can spread to transgenic promoters. However, de novo histone H3 acetylation and H3 K4 methylation at a transgenic promoter in a nonpermissive chromatin region are stochastic, leading to variegated transgene expression. Moreover, nonpermissive chromatin progressively silences a transgene, an event that is accompanied by the reduction of H3 K4 methylation and H3 acetylation levels at the transgenic promoter. These repressive effects of nonpermissive chromatin cannot be completely countered by strong transcription activators, indicating the dominance of the chromatin effects. We therefore propose a model in which histone H3 acetylation and H3 K4 methylation localized to discrete sites in the mammalian genome mark distinct chromatin functions that dictate transgene expression or silencing.


Author(s):  
Quen J. Cheng ◽  
Sho Ohta ◽  
Katherine M. Sheu ◽  
Roberto Spreafico ◽  
Adewunmi Adelaja ◽  
...  

SummaryThe epigenome defines the cell type, but also shows plasticity that enables cells to tune their gene expression potential to the context of extracellular cues. This is evident in immune sentinel cells such as macrophages, which can respond to pathogens and cytokines with phenotypic shifts that are driven by epigenomic reprogramming1. Recent studies indicate that this reprogramming arises from the activity of transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), which binds not only to available enhancers but may produce de novo enhancers in previously silent areas of the genome2. Here, we show that NFκB reprograms the macrophage epigenome in a stimulus-specific manner, in response only to a subset of pathogen-derived stimuli. The basis for these surprising differences lies in the stimulus-specific temporal dynamics of NFκB activity. Testing predictions of a mathematical model of nucleosome interactions, we demonstrate through live cell imaging and genetic perturbations that NFκB promotes open chromatin and formation of de novo enhancers most strongly when its activity is non-oscillatory. These de novo enhancers result in the activation of additional response genes. Our study demonstrates that the temporal dynamics of NFκB activity, which encode ligand identity3, can be decoded by the epigenome through de novo enhancer formation. We propose a mechanistic paradigm in which the temporal dynamics of transcription factors are a key determinant of their capacity to control epigenomic reprogramming, thus enabling the formation of stimulus-specific memory in innate immune sentinel cells.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Patrick Driguez ◽  
Salim Bougouffa ◽  
Karen Carty ◽  
Alexander Putra ◽  
Kamel Jabbari ◽  
...  

AbstractCurrently, different sequencing platforms are used to generate plant genomes and no workflow has been properly developed to optimize time, cost, and assembly quality. We present LeafGo, a complete de novo plant genome workflow, that starts from tissue and produces genomes with modest laboratory and bioinformatic resources in approximately 7 days and using one long-read sequencing technology. LeafGo is optimized with ten different plant species, three of which are used to generate high-quality chromosome-level assemblies without any scaffolding technologies. Finally, we report the diploid genomes of Eucalyptus rudis and E. camaldulensis and the allotetraploid genome of Arachis hypogaea.


2020 ◽  
Vol 48 (12) ◽  
pp. 6685-6698 ◽  
Author(s):  
Xinyan Zhang ◽  
Meixia Zhao ◽  
Donald R McCarty ◽  
Damon Lisch

Abstract Transposable elements (TEs) are ubiquitous DNA segments capable of moving from one site to another within host genomes. The extant distributions of TEs in eukaryotic genomes have been shaped by both bona fide TE integration preferences in eukaryotic genomes and by selection following integration. Here, we compare TE target site distribution in host genomes using multiple de novo transposon insertion datasets in both plants and animals and compare them in the context of genome-wide transcriptional landscapes. We showcase two distinct types of transcription-associated TE targeting strategies that suggest a process of convergent evolution among eukaryotic TE families. The integration of two precision-targeting elements are specifically associated with initiation of RNA Polymerase II transcription of highly expressed genes, suggesting the existence of novel mechanisms of precision TE targeting in addition to passive targeting of open chromatin. We also highlight two features that can facilitate TE survival and rapid proliferation: tissue-specific transposition and minimization of negative impacts on nearby gene function due to precision targeting.


2004 ◽  
Vol 24 (20) ◽  
pp. 9152-9164 ◽  
Author(s):  
Arunadevi Yarragudi ◽  
Tsuyoshi Miyake ◽  
Rong Li ◽  
Randall H. Morse

ABSTRACT Autonomously replicating sequence binding factor 1 (ABF1) and repressor/activator protein 1 (RAP1) from budding yeast are multifunctional, site-specific DNA-binding proteins, with roles in gene activation and repression, replication, and telomere structure and function. Previously we have shown that RAP1 can prevent nucleosome positioning in the vicinity of its binding site and have provided evidence that this ability to create a local region of “open” chromatin contributes to RAP1 function at the HIS4 promoter by facilitating binding and activation by GCN4. Here we examine and directly compare to that of RAP1 the ability of ABF1 to create a region of open chromatin near its binding site and to contribute to activated transcription at the HIS4, ADE5,7, and HIS7 promoters. ABF1 behaves similarly to RAP1 in these assays, but it shows some subtle differences from RAP1 in the character of the open chromatin region near its binding site. Furthermore, although the two factors can similarly enhance activated transcription at the promoters tested, RAP1 binding is continuously required for this enhancement, but ABF1 binding is not. These results indicate that ABF1 and RAP1 achieve functional similarity in part via mechanistically distinct pathways.


2021 ◽  
Author(s):  
Chenshen Huang ◽  
Ning Wang ◽  
Na Zhang ◽  
Zhizhan Ni ◽  
Xiaohong Liu ◽  
...  

Background: Accumulating evidence suggests that inflammation-related genes may play key roles in tumor immune evasion. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint involved in mediating antitumor immunity. We performed multi-omics analysis to explore key inflammation-related genes affecting the transcriptional regulation of PD-L1 expression. Methods: The open chromatin region of the PD-L1 promoter was mapped using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles. Correlation analysis of epigenetic data (ATAC-seq) and transcriptome data (RNA-seq) were performed to identify inflammation-related transcription factors whose expression levels were correlated with the chromatin accessibility of the PD-L1 promoter. Chromatin immunoprecipitation sequencing (ChIP-seq) profiles were used to confirm the physical binding of the TF STAT2 and the predicted binding regions. We also confirmed the results of the bioinformatics analysis with cell experiments. Results: We identified chr9:5449463-5449962 and chr9:5450250-5450749 as reproducible open chromatin regions in the PD-L1 promoter. Moreover, we observed a correlation between STAT2 expression and the accessibility of the aforementioned regions. Furthermore, we confirmed its physical binding through ChIP-seq profiles and demonstrated the regulation of PD-L1 by STAT2 overexpression in vitro. Multiple databases were also used for the validation of the results. Conclusion: Our study identified STAT2 as a direct upstream TF regulating PD-L1 expression. The interaction of STAT2 and PD-L1 might be associated with tumor immune evasion in cancers, suggesting the potential value for tumor treatment.


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