scholarly journals Chromatin variation associated with liver metabolism is mediated by transposable elements

2016 ◽  
Author(s):  
Juan Du ◽  
Amy Leung ◽  
Candi Trac ◽  
Brian W. Parks ◽  
Aldons J. Lusis ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transposable Elements ◽  
Complex Traits ◽  
Phenotypic Diversity ◽  
Enrichment Analysis ◽  
Chromatin Accessibility ◽  
Genomic Region ◽  
Long Interspersed Nuclear Elements ◽  
Accessible Chromatin ◽  
High Sucrose

AbstractBackgroundFunctional regulatory regions in eukaryotic genomes are characterized by the disruption of nucleosomes leading to accessible chromatin. The modulation of chromatin accessibility is one of the key mediators of transcriptional regulation and variation in chromatin accessibility across individuals has been liked to complex traits and disease susceptibility. While mechanisms responsible for chromatin variation across individuals have been investigated, the overwhelming majority of chromatin variation remains unexplained. Furthermore, the processes through which the variation of chromatin accessibility contributes to phenotypic diversity remain poorly understood.ResultsWe profiled chromatin accessibility in liver from seven strains of mice with phenotypic diversity in response to a high-fat/high-sucrose (HF/HS) diet and identified reproducible chromatin variation across the genome. We found that sites of variable chromatin accessibility were more likely to coincide with particular classes of transposable elements (TEs) than sites with common chromatin features. Evolutionarily younger long interspersed nuclear elements (LINEs) are particularly enriched for variable chromatin sites. These younger LINEs are enriched for binding sites of immune-associated transcription factors, whereas older LINEs are enriched for liver-specific transcription factors. Genomic region enrichment analysis indicates that variable chromatin sites at TEs contribute to liver metabolic pathways. Finally, we show that polymorphism of TEs and differential DNA methylation at TEs can both contribute to chromatin variation.ConclusionsOur results demonstrate specific classes of TEs contribute to chromatin accessibility variation across strains of mice that display phenotypic diversity in response to a HF/HS diet. These results indicate that regulatory variation at TEs is an important contributor to phenotypic variation among populations.

scholarly journals Specific enhancer selection by IRF3, IRF5 and IRF9 is determined by ISRE half-sites, 5′ and 3′ flanking bases, collaborating transcription factors and the chromatin environment in a combinatorial fashion

2019 ◽  
Vol 48 (2) ◽  
pp. 589-604 ◽  
Author(s):  
Mária Csumita ◽  
Attila Csermely ◽  
Attila Horvath ◽  
Gergely Nagy ◽  
Fanny Monori ◽  
...  
Keyword(s):  
Machine Learning ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Inflammatory Responses ◽  
Enrichment Analysis ◽  
Chromatin Accessibility ◽  
Machine Learning Method ◽  
Learning Method ◽  
Overlapping Sets ◽  
Accessible Chromatin

Abstract IRF3, IRF5 and IRF9 are transcription factors, which play distinct roles in the regulation of antiviral and inflammatory responses. The determinants that mediate IRF-specific enhancer selection are not fully understood. To uncover regions occupied predominantly by IRF3, IRF5 or IRF9, we performed ChIP-seq experiments in activated murine dendritic cells. The identified regions were analysed with respect to the enrichment of DNA motifs, the interferon-stimulated response element (ISRE) and ISRE half-site variants, and chromatin accessibility. Using a machine learning method, we investigated the predictability of IRF-dominance. We found that IRF5-dominant regions differed fundamentally from the IRF3- and IRF9-dominant regions: ISREs were rare, while the NFKB motif and special ISRE half-sites, such as 5′-GAGA-3′ and 5′-GACA-3′, were enriched. IRF3- and IRF9-dominant regions were characterized by the enriched ISRE motif and lower frequency of accessible chromatin. Enrichment analysis and the machine learning method uncovered the features that favour IRF3 or IRF9 dominancy (e.g. a tripartite form of ISRE and motifs for NF-κB for IRF3, and the GAS motif and certain ISRE variants for IRF9). This study contributes to our understanding of how IRF members, which bind overlapping sets of DNA sequences, can initiate signal-dependent responses without activating superfluous or harmful programmes.

scholarly journals Assessing the regulatory potential of transposable elements using chromatin accessibility profiles of maize transposons

Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
Author(s):  
Jaclyn M Noshay ◽  
Alexandre P Marand ◽  
Sarah N Anderson ◽  
Peng Zhou ◽  
Maria Katherine Mejia Guerra ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Allelic Variation ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Transcriptional Responses ◽  
Maize Genotypes ◽  
Show Evidence ◽  
Regulatory Potential ◽  
Dna Regulatory Elements ◽  
Accessible Chromatin

Abstract Transposable elements (TEs) have the potential to create regulatory variation both through the disruption of existing DNA regulatory elements and through the creation of novel DNA regulatory elements. In a species with a large genome, such as maize, many TEs interspersed with genes create opportunities for significant allelic variation due to TE presence/absence polymorphisms among individuals. We used information on putative regulatory elements in combination with knowledge about TE polymorphisms in maize to identify TE insertions that interrupt existing accessible chromatin regions (ACRs) in B73 as well as examples of polymorphic TEs that contain ACRs among four inbred lines of maize including B73, Mo17, W22, and PH207. The TE insertions in three other assembled maize genomes (Mo17, W22, or PH207) that interrupt ACRs that are present in the B73 genome can trigger changes to the chromatin, suggesting the potential for both genetic and epigenetic influences of these insertions. Nearly 20% of the ACRs located over 2 kb from the nearest gene are located within an annotated TE. These are regions of unmethylated DNA that show evidence for functional importance similar to ACRs that are not present within TEs. Using a large panel of maize genotypes, we tested if there is an association between the presence of TE insertions that interrupt, or carry, an ACR and the expression of nearby genes. While most TE polymorphisms are not associated with expression for nearby genes, the TEs that carry ACRs exhibit enrichment for being associated with higher expression of nearby genes, suggesting that these TEs may contribute novel regulatory elements. These analyses highlight the potential for a subset of TEs to rewire transcriptional responses in eukaryotic genomes.

scholarly journals A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing

2021 ◽  
Author(s):  
Chao Yuan ◽  
Zengkui Lu ◽  
Tingting Guo ◽  
Yaojing Yue ◽  
Xijun Wang ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Complex Traits ◽  
Phenotypic Diversity ◽  
Average Length ◽  
Global Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Nutrient Metabolism ◽  
Relaxin Family

Abstract Background Copy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, economically important traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing.Results A total of 1,747,604 CNVs were detected in this study, and 7,228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4,307.17 bp. “Deletion” events took place more frequently than “duplication” or “both” events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39%–55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1,855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective sweep of CNVRs, and it was found that the relaxin family peptide receptor 2 (RXFP2) gene was strongly influenced by selection.Conclusions In summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.

scholarly journals Establishment of chromatin accessibility by the conserved transcription factor Grainy head is developmentally regulated

2019 ◽  
Author(s):  
Markus Nevil ◽  
Tyler J. Gibson ◽  
Constantine Bartolutti ◽  
Anusha Iyengar ◽  
Melissa M Harrison
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Chromatin Accessibility ◽  
Mitotic Chromosomes ◽  
Developmentally Regulated ◽  
Regulatory Modules ◽  
Pioneer Factor ◽  
Pioneer Factors ◽  
Coordinate Changes ◽  
Accessible Chromatin

AbstractThe dramatic changes in gene expression required for development necessitate the establishment of cis-regulatory modules defined by regions of accessible chromatin. Pioneer transcription factors have the unique property of binding closed chromatin and facilitating the establishment of these accessible regions. Nonetheless, much of how pioneer transcription factors coordinate changes in chromatin accessibility during development remains unknown. To determine whether pioneer-factor function is intrinsic to the protein or whether pioneering activity is developmentally modulated, we studied the highly conserved, essential transcription factor, Grainy head (Grh). Grh is expressed throughout Drosophila development and functions as a pioneer factor in the larvae. We demonstrated that Grh remains bound to condensed mitotic chromosomes, a property shared with other pioneer factors. By assaying chromatin accessibility in embryos lacking either maternal or zygotic Grh at three stages of development, we discovered that Grh is not required for chromatin accessibility in early embryogenesis, in contrast to its essential functions later in development. Our data reveal that the pioneering activity of Grh is temporally regulated and is likely influenced by additional factors expressed at a given developmental stage.

scholarly journals A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing

2020 ◽  
Author(s):  
Chao Yuan ◽  
Zengkui Lu ◽  
Tingting Guo ◽  
Yaojing Yue ◽  
Xijun Wang ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Complex Traits ◽  
Phenotypic Diversity ◽  
Average Length ◽  
Global Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Economic Traits ◽  
Nutrient Metabolism ◽  
Relaxin Family

Abstract Background: Copy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, important economic traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing. Results: A total of 1747604 CNVs were detected in this study, and 7228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4307.17 bp. “Deletion” events took place more frequently than “duplication” or “both” events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39%–55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective elimination of CNVRs, and it was found that the relaxin family peptide receptor 2 ( RXFP2 ) gene was strongly influenced by selection. Conclusions: In summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.

scholarly journals ATF3 drives senescence by reconstructing accessible chromatin profiles

2020 ◽  
Author(s):  
Chao Zhang ◽  
Xuebin Zhang ◽  
Yiting Guan ◽  
Xiaoke Huang ◽  
Lijun Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Regulatory Mechanism ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Dynamic Landscape ◽  
Intergenic Regions ◽  
Senescence Program ◽  
Accessible Chromatin

AbstractChromatin architecture and gene expression profile undergo tremendous reestablishment during senescence. However, the regulatory mechanism between chromatin reconstruction and gene expression in senescence remain elusive. The chromatin accessibility is an excellent perspective to reveal the latent regulatory elements. Thus, we depicted the landscapes of chromatin accessibility and gene expression during HUVECs senescence. We found that chromatin accessibilities are re-distributed during senescence. The senescence related increased accessible regions (IARs) and the decreased accessible regions (DARs) are mainly distributed in distal intergenic regions. The DARs are correlated with the function declines caused by senescence, whereas the IARs are involved in the regulation for senescence program. Moreover, the heterochromatin contributes most of IARs in senescent cells. We identified that the AP-1 transcription factors, especially ATF3 is responsible for driving chromatin accessibility reconstruction in IARs. In particular, DNA methylation is negatively correlated with chromatin accessibility during senescence. AP-1 motifs with low DNA methylation may improve their binding affinity in IARs and further opens the chromatin nearby. Our results described a dynamic landscape of chromatin accessibility whose remodeling contributes to the senescence program. And we identified a cellular senescence regulator, AP-1, which promotes senescence through organizing the accessibility profile in IARs.

scholarly journals A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing

2019 ◽  
Author(s):  
chao yuan ◽  
Zengkui Lu ◽  
Tingting Guo ◽  
yaojing Yue ◽  
Xijun Wang ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Complex Traits ◽  
Phenotypic Diversity ◽  
Average Length ◽  
Global Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Economic Traits ◽  
Nutrient Metabolism

Abstract Background Copy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, important economic traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing.Results A total of 1747604 CNVs were detected in this study, and 7228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4307.17 bp. “Deletion” events took place more frequently than “duplication” or “both” events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39%–55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective elimination of CNVRs, and it was found that the RXFP2 gene was strongly influenced by selection.Conclusions In summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.

scholarly journals Identification of Chromatin Accessibility During The Early Stage of Pig SCNT Embryo Reprogramming by ATAC-Seq

2020 ◽  
Author(s):  
Xue Zhang ◽  
Juan Li ◽  
Ruixin Tao ◽  
Aiwen Jiang ◽  
Changyin Zhou ◽  
...  
Keyword(s):  
Histone Modification ◽  
Large Scale ◽  
Transcriptional Activity ◽  
Early Stage ◽  
Enrichment Analysis ◽  
Chromatin Accessibility ◽  
Nuclear Transplantation ◽  
Dynamic Changes ◽  
Accessible Chromatin ◽  
Insight Into

Abstract Background: Somatic cell nuclear transplantation (SCNT) can transform highly differentiated donor nuclei into pluripotent nuclei through the large-scale reprogramming of chromatin. The reprogramming of chromatin has been documented to take place in the first few hours after SCNT embryo activation. Thus, studies that characterize dynamic changes in chromatin during the first few hours after embryo activation could provide insight into the mechanism and significance of genome-wide reprogramming. However, few studies have examined the epigenetic remodeling of reconstructed embryos during the early stage of reprogramming.Results: We conducted ATAC-seq on 50 porcine SCNT-HMC embryos and 50 parthenogenetic activation (PA) embryos 10 h after activation. Along with pig embryonic fibroblast (PEF) ATAC-seq data, we found low levels of chromatin accessibility and gene transcription in SCNT and PA embryos. Moreover, PEF genes and the X chromosome became inaccessible during embryo reprogramming. GO enrichment analysis revealed that the molecular functions related to accessible chromatin in embryos primarily included transcriptional regulatory activity and SMAD binding. The differentially accessible chromatin sites between SCNT and PEF were primarily related to transcriptional activity and histone modification.Conclusions: Despite the tight chromatin structure during the early stage of embryo reprogramming, some accessible chromatin sites, which were primarily distributed in the intergenic region, were still detected. Dynamic changes in chromatin accessibility during reprogramming were primarily related to transcriptional activity and histone modification. Generally, this study provided new insight into the dynamics and importance of chromatin accessibility during the early stages of embryo reprogramming.

scholarly journals A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing

2020 ◽  
Author(s):  
Chao Yuan ◽  
Zengkui Lu ◽  
Tingting Guo ◽  
Yaojing Yue ◽  
Xijun Wang ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Complex Traits ◽  
Phenotypic Diversity ◽  
Average Length ◽  
Global Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Economic Traits ◽  
Nutrient Metabolism ◽  
Relaxin Family

Abstract BackgroundCopy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, important economic traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing.ResultsA total of 1,747,604 CNVs were detected in this study, and 7,228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4,307.17 bp. “Deletion” events took place more frequently than “duplication” or “both” events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39%–55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1,855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective sweep of CNVRs, and it was found that the relaxin family peptide receptor 2 (RXFP2) gene was strongly influenced by selection.ConclusionsIn summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.

scholarly journals A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chao Yuan ◽  
Zengkui Lu ◽  
Tingting Guo ◽  
Yaojing Yue ◽  
Xijun Wang ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Complex Traits ◽  
Phenotypic Diversity ◽  
Average Length ◽  
Global Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Nutrient Metabolism ◽  
Relaxin Family

Abstract Background Copy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, economically important traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing. Results A total of 1,747,604 CNVs were detected in this study, and 7228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4307.17 bp. “Deletion” events took place more frequently than “duplication” or “both” events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39–55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective sweep of CNVRs, and it was found that the relaxin family peptide receptor 2 (RXFP2) gene was strongly influenced by selection. Conclusions In summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.

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