scholarly journals A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiao-Long Cui ◽  
Ji Nie ◽  
Jeremy Ku ◽  
Urszula Dougherty ◽  
Diana C. West-Szymanski ◽  
...  
Keyword(s):  
Human Tissue ◽  
Tissue Specificity ◽  
Dna Demethylation ◽  
Tissue Type ◽  
Specific Gene ◽  
Mammalian Development ◽  
Tissue Specific ◽  
Genome Wide ◽  
Organ Systems

AbstractDNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a mark to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe the development of a 5hmC tissue map by characterizing the genomic distributions of 5hmC in 19 human tissues derived from ten organ systems. Subsequent sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separates samples by tissue type. Further comparison of the 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC is preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, the results provide an extensive 5hmC map across diverse human tissue types that suggests a potential role of 5hmC in tissue-specific development; as well as a resource to facilitate future studies of DNA demethylation in pathogenesis and the development of 5hmC as biomarkers.

scholarly journals Identification of key tissue-specific, biological processes by integrating enhancer information in maize gene regulatory networks

2020 ◽  
Author(s):  
Maud Fagny ◽  
Marieke Lydia Kuijjer ◽  
Maike Stam ◽  
Johann Joets ◽  
Olivier Turc ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Binding Sites ◽  
Regulatory Network ◽  
Tissue Specificity ◽  
Target Genes ◽  
Specific Gene ◽  
Tissue Specific ◽  
Genome Wide ◽  
Gene Regulatory

AbstractEnhancers are important regulators of gene expression during numerous crucial processes including tissue differentiation across development. In plants, their recent molecular characterization revealed their capacity to activate the expression of several target genes through the binding of transcription factors. Nevertheless, identifying these target genes at a genome-wide level remains a challenge, in particular in species with large genomes, where enhancers and target genes can be hundreds of kilobases away. Therefore, the contribution of enhancers to regulatory network is still poorly understood in plants. In this study, we investigate the enhancer-driven regulatory network of two maize tissues at different stages: leaves at seedling stage and husks (bracts) at flowering. Using a systems biology approach, we integrate genomic, epigenomic and transcriptomic data to model the regulatory relationship between transcription factors and their potential target genes. We identify regulatory modules specific to husk and V2-IST, and show that they are involved in distinct functions related to the biology of each tissue. We evidence enhancers exhibiting binding sites for two distinct transcription factor families (DOF and AP2/ERF) that drive the tissue-specificity of gene expression in seedling immature leaf and husk. Analysis of the corresponding enhancer sequences reveals that two different transposable element families (TIR transposon Mutator and MITE Pif/Harbinger) have shaped the regulatory network in each tissue, and that MITEs have provided new transcription factor binding sites that are involved in husk tissue-specificity.SignificanceEnhancers play a major role in regulating tissue-specific gene expression in higher eukaryotes, including angiosperms. While molecular characterization of enhancers has improved over the past years, identifying their target genes at the genome-wide scale remains challenging. Here, we integrate genomic, epigenomic and transcriptomic data to decipher the tissue-specific gene regulatory network controlled by enhancers at two different stages of maize leaf development. Using a systems biology approach, we identify transcription factor families regulating gene tissue-specific expression in husk and seedling leaves, and characterize the enhancers likely to be involved. We show that a large part of maize enhancers is derived from transposable elements, which can provide novel transcription factor binding sites crucial to the regulation of tissue-specific biological functions.

scholarly journals Novel lincRNA Discovery and Tissue-Specific Gene Expression across 30 Normal Human Tissues

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 614
Author(s):  
Xianfeng Chen ◽  
Zhifu Sun
Keyword(s):  
Brain Regions ◽  
Tissue Type ◽  
Specific Gene ◽  
The Novel ◽  
Rna Seq ◽  
Specific Expression ◽  
Tissue Specific ◽  
Genome Wide ◽  
Gene Transcripts ◽  
Normal Human

Long non-coding RNAs (lncRNAs) are a large class of gene transcripts that do not code proteins; however, their functions are largely unknown and many new lncRNAs are yet to be discovered. Taking advantage of our previously developed, super-fast, novel lncRNA discovery pipeline, UClncR, and rich resources of GTEx RNA-seq data, we performed systematic novel lincRNA discovery for over 8000 samples across 30 tissue types. We conducted novel detection for each major tissue type first and then consolidated the novel discoveries from all tissue types. These novel lincRNs were profiled and analyzed along with known genes to identify tissue-specific genes in 30 major human tissue types. Thirteen sub-brain regions were also analyzed in a similar manner. Our analysis revealed thousands to tens of thousands of novel lincRNAs for each tissue type. These lincRNAs could define each tissue type’s identity and demonstrated their reliability and tissue-specific expression. Tissue-specific genes were identified for each major tissue type and sub-brain region. The tissue-specific genes clearly defined each respective tissue’s unique function and could be used to expand the interpretation of non-coding SNPs from genome-wide association (GWAS) studies.

scholarly journals Classification of topological domains based on gene expression and regulation

Genome ◽  
2013 ◽  
Vol 56 (7) ◽  
pp. 415-423 ◽  
Author(s):  
Jingjing Zhao ◽  
Hongbo Shi ◽  
Nadav Ahituv
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Tissue Type ◽  
Specific Gene ◽  
Gene Expression And Regulation ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
Topological Domains ◽  
Tissue Specific ◽  
Mouse Tissues

Tissue-specific gene expression is thought to be one of the major forces shaping mammalian gene order. A recent study that used whole-genome chromosome conformation assays has shown that the mammalian genome is divided into specific topological domains that are shared between different tissues and organisms. Here, we wanted to assess whether gene expression and regulation are involved in shaping these domains and can be used to classify them. We analyzed gene expression and regulation levels in these domains by using RNA-seq and enhancer-associated ChIP-seq datasets for 17 different mouse tissues. We found 162 domains that are active (high gene expression and regulation) in all 17 tissues. These domains are significantly shorter, contain less repeats, and have more housekeeping genes. In contrast, we found 29 domains that are inactive (low gene expression and regulation) in all analyzed tissues and are significantly longer, have more repeats, and gene deserts. Tissue-specific active domains showed some correlation with tissue-type and gene ontology. Domain temporal gene regulation and expression differences also displayed some gene ontology terms fitting their temporal function. Combined, our results provide a catalog of shared and tissue-specific topological domains and suggest that gene expression and regulation could have a role in shaping them.

Salt-Responsive Genes are Differentially Regulated at the Chromatin Levels Between Seedlings and Roots in Rice

2019 ◽  
Vol 60 (8) ◽  
pp. 1790-1803 ◽  
Author(s):  
Dongyang Zheng ◽  
Lei Wang ◽  
Lifen Chen ◽  
Xiucai Pan ◽  
Kande Lin ◽  
...  
Keyword(s):  
Salt Tolerance ◽  
Differential Expression ◽  
Mutual Exclusion ◽  
Positive Association ◽  
Specific Gene ◽  
Epigenetic Mechanisms ◽  
Chromatin Modifications ◽  
Tissue Specific ◽  
Underlying Mechanisms

Abstract The elucidation of epigenetic responses of salt-responsive genes facilitates understanding of the underlying mechanisms that confer salt tolerance in rice. However, it is still largely unknown how epigenetic mechanisms are associated with the expression of salt-responsive genes in rice and other crops. In this study, we reported tissue-specific gene expression and tissue-specific changes in chromatin modifications or signatures between seedlings and roots in response to salt treatment. Our study indicated that among six of individual mark examined (H3K4me3, H3K27me3, H4K12ac, H3K9ac, H3K27ac and H3K36me3), a positive association between salt-related changes in histone marks and the expression of differentially expressed genes (DEGs) was observed only for H3K9ac and H4K12ac in seedlings and H3K36me3 in roots. In contrast, chromatin states (CSs) with combinations of six histone modification marks played crucial roles in the differential expression of salt-responsive genes between seedlings and roots. Most importantly, CS7 containing the bivalent marks H3K4me3 and H3K27me3, with a mutual exclusion of functions with each other, displayed distinct functions in the expression of DEGs in both tissues. Specifically, H3K27me3 in CS7 mainly suppressed the expression of DEGs in roots, while H3K4me3 affected the expression of down- and up-regulated genes, possibly by antagonizing the repressive role of H3K27me3 in seedlings. Our findings indicate distinct impacts of the CSs on the differential expression of salt-responsive genes between seedlings and roots in rice, which provides an important background for understanding chromatin-based epigenetic mechanisms that might confer salt tolerance in plants.

scholarly journals Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics

2013 ◽  
Vol 13 (2) ◽  
pp. 397-406 ◽  
Author(s):  
Linn Fagerberg ◽  
Björn M. Hallström ◽  
Per Oksvold ◽  
Caroline Kampf ◽  
Dijana Djureinovic ◽  
...  
Keyword(s):  
Human Tissue ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Genome Wide

scholarly journals Understanding Tissue-specific Gene Regulation

2017 ◽  
Author(s):  
Abhijeet R. Sonawane ◽  
John Platig ◽  
Maud Fagny ◽  
Cho-Yi Chen ◽  
Joseph N. Paulson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Control ◽  
Tissue Specificity ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
Gene Set Enrichment Analysis ◽  
Specific Gene ◽  
Tissue Specific ◽  
Network Nodes ◽  
Transcription Factor Expression

Although all human tissues carry out common processes, tissues are distinguished by gene expres-sion patterns, implying that distinct regulatory programs control tissue-specificity. In this study, we investigate gene expression and regulation across 38 tissues profiled in the Genotype-Tissue Expression project. We find that network edges (transcription factor to target gene connections) have higher tissue-specificity than network nodes (genes) and that regulating nodes (transcription factors) are less likely to be expressed in a tissue-specific manner as compared to their targets (genes). Gene set enrichment analysis of network targeting also indicates that regulation of tissue-specific function is largely independent of transcription factor expression. In addition, tissue-specific genes are not highly targeted in their corresponding tissue-network. However, they do assume bottleneck positions due to variability in transcription factor targeting and the influence of non-canonical regulatory interactions. These results suggest that tissue-specificity is driven by context-dependent regulatory paths, providing transcriptional control of tissue-specific processes.

scholarly journals Epigenomic co-localization and co-evolution reveal a key role for 5hmC as a communication hub in the chromatin network of ESCs

2014 ◽  
Author(s):  
David Juan ◽  
Juliane Perner ◽  
Enrique Carrillo de Santa Pau ◽  
Simone Marsili ◽  
David Ochoa ◽  
...  
Keyword(s):  
Communication Network ◽  
Dna Demethylation ◽  
Communication Model ◽  
Evolutionary Analysis ◽  
Manual Annotation ◽  
Nucleosome Remodeling ◽  
Location Data ◽  
Genome Wide ◽  
Related Proteins

Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC) is the most influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC colocalizes with specific interactors shows that each interaction points to chromatin remodelling, stemness, differentiation or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs.

scholarly journals Recent evolution of a TET-controlled and DPPA3/STELLA-driven pathway of passive DNA demethylation in mammals

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Christopher B. Mulholland ◽  
Atsuya Nishiyama ◽  
Joel Ryan ◽  
Ryohei Nakamura ◽  
Merve Yiğit ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Large Scale ◽  
Unique Feature ◽  
Mammalian Species ◽  
Dna Demethylation ◽  
Evolutionary Divergence ◽  
Mammalian Development ◽  
Active Demethylation ◽  
Global Hypomethylation ◽  
Genome Wide

AbstractGenome-wide DNA demethylation is a unique feature of mammalian development and naïve pluripotent stem cells. Here, we describe a recently evolved pathway in which global hypomethylation is achieved by the coupling of active and passive demethylation. TET activity is required, albeit indirectly, for global demethylation, which mostly occurs at sites devoid of TET binding. Instead, TET-mediated active demethylation is locus-specific and necessary for activating a subset of genes, including the naïve pluripotency and germline marker Dppa3 (Stella, Pgc7). DPPA3 in turn drives large-scale passive demethylation by directly binding and displacing UHRF1 from chromatin, thereby inhibiting maintenance DNA methylation. Although unique to mammals, we show that DPPA3 alone is capable of inducing global DNA demethylation in non-mammalian species (Xenopus and medaka) despite their evolutionary divergence from mammals more than 300 million years ago. Our findings suggest that the evolution of Dppa3 facilitated the emergence of global DNA demethylation in mammals.

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