scholarly journals Complex Analysis of Retroposed Genes’ Contribution to Human Genome, Proteome and Transcriptome

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 542
Author(s):  
Magdalena Regina Kubiak ◽  
Michał Wojciech Szcześniak ◽  
Izabela Makałowska
Keyword(s):  
Complex Analysis ◽  
Genomic Sequence ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Protein Domain ◽  
Gene Duplications ◽  
Protein Coding ◽  
Spatio Temporal ◽  
Recombination Hot Spots ◽  
Cis And Trans

Gene duplication is a major driver of organismal evolution. One of the main mechanisms of gene duplications is retroposition, a process in which mRNA is first transcribed into DNA and then reintegrated into the genome. Most gene retrocopies are depleted of the regulatory regions. Nevertheless, examples of functional retrogenes are rapidly increasing. These functions come from the gain of new spatio-temporal expression patterns, imposed by the content of the genomic sequence surrounding inserted cDNA and/or by selectively advantageous mutations, which may lead to the switch from protein coding to regulatory RNA. As recent studies have shown, these genes may lead to new protein domain formation through fusion with other genes, new regulatory RNAs or other regulatory elements. We utilized existing data from high-throughput technologies to create a complex description of retrogenes functionality. Our analysis led to the identification of human retroposed genes that substantially contributed to transcriptome and proteome. These retrocopies demonstrated the potential to encode proteins or short peptides, act as cis- and trans- Natural Antisense Transcripts (NATs), regulate their progenitors’ expression by competing for the same microRNAs, and provide a sequence to lncRNA and novel exons to existing protein-coding genes. Our study also revealed that retrocopies, similarly to retrotransposons, may act as recombination hot spots. To our best knowledge this is the first complex analysis of these functions of retrocopies.

scholarly journals Transcriptional regulation of metabolism in disease: From transcription factors to epigenetics

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5062 ◽  
Author(s):  
Liam J. Hawkins ◽  
Rasha Al-attar ◽  
Kenneth B. Storey
Keyword(s):  
Transcriptional Regulation ◽  
Genomic Sequence ◽  
Regulatory Elements ◽  
Regulatory Pathways ◽  
Transcriptional Dysregulation ◽  
Disease States ◽  
Specific Subset ◽  
Transcriptional Regulatory ◽  
Cis And Trans ◽  
Or Genes

Every cell in an individual has largely the same genomic sequence and yet cells in different tissues can present widely different phenotypes. This variation arises because each cell expresses a specific subset of genomic instructions. Control over which instructions, or genes, are expressed is largely controlled by transcriptional regulatory pathways. Each cell must assimilate a huge amount of environmental input, and thus it is of no surprise that transcription is regulated by many intertwining mechanisms. This large regulatory landscape means there are ample possibilities for problems to arise, which in a medical context means the development of disease states. Metabolism within the cell, and more broadly, affects and is affected by transcriptional regulation. Metabolism can therefore contribute to improper transcriptional programming, or pathogenic metabolism can be the result of transcriptional dysregulation. Here, we discuss the established and emerging mechanisms for controling transcription and how they affect metabolism in the context of pathogenesis. Cis- and trans-regulatory elements, microRNA and epigenetic mechanisms such as DNA and histone methylation, all have input into what genes are transcribed. Each has also been implicated in diseases such as metabolic syndrome, various forms of diabetes, and cancer. In this review, we discuss the current understanding of these areas and highlight some natural models that may inspire future therapeutics.

scholarly journals Characterisation and functional predictions of canine long non-coding RNAs

2018 ◽  
Author(s):  
Céline Le Béguec ◽  
Valentin Wucher ◽  
Lætitia Lagoutte ◽  
Edouard Cadieu ◽  
Nadine Botherel ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Domestic Dog ◽  
Tissue Type ◽  
Protein Coding ◽  
Functional Roles ◽  
Integrative Study ◽  
Non Coding Rnas ◽  
Biological Functionality

AbstractLong non-coding RNAs (lncRNAs) are a family of heterogeneous RNAs that play major roles in multiple biological processes. We recently identified an extended repertoire of more than 10,000 lncRNAs of the domestic dog however, predicting their biological functionality remains challenging. In this study, we have characterised the expression profiles of 10,444 canine lncRNAs in 26 distinct tissue types, representing various anatomical systems. We showed that lncRNA expressions are mainly clustered by tissue type and we highlighted that 44% of canine lncRNAs are expressed in a tissue-specific manner. We further demonstrated that tissue-specificity correlates with specific families of canine transposable elements. In addition, we identified more than 900 conserved dog-human lncRNAs for which we show their overall reproducible expression patterns between dog and humans through comparative transcriptomics. Finally, co-expression analyses of lncRNA and neighbouring protein-coding genes identified more than 3,400 canine lncRNAs, suggesting that functional roles of these lncRNAs act as regulatory elements. Altogether, this genomic and transcriptomic integrative study of lncRNAs constitutes a major resource to investigate genotype to phenotype relationships and biomedical research in the dog species.

scholarly journals Genome-Wide Identification and Analysis of the NPR1-Like Gene Family in Bread Wheat and Its Relatives

2019 ◽  
Vol 20 (23) ◽  
pp. 5974 ◽  
Author(s):  
Xian Liu ◽  
Zhiguo Liu ◽  
Xinhui Niu ◽  
Qian Xu ◽  
Long Yang
Keyword(s):  
Gene Family ◽  
Bread Wheat ◽  
Plant Immunity ◽  
Expression Patterns ◽  
Functional Characterization ◽  
Aegilops Tauschii ◽  
Regulatory Elements ◽  
Protein Domain ◽  
Chromosomal Distribution ◽  
Specific Expression

NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), and its paralogues NPR3 and NPR4, are bona fide salicylic acid (SA) receptors and play critical regulatory roles in plant immunity. However, comprehensive identification and analysis of the NPR1-like gene family had not been conducted so far in bread wheat and its relatives. Here, a total of 17 NPR genes in Triticum aestivum, five NPR genes in Triticum urartu, 12 NPR genes in Triticum dicoccoides, and six NPR genes in Aegilops tauschii were identified using bioinformatics approaches. Protein properties of these putative NPR1-like genes were also described. Phylogenetic analysis showed that the 40 NPR1-like proteins, together with 40 NPR1-related proteins from other plant species, were clustered into three major clades. The TaNPR1-like genes belonging to the same Arabidopsis subfamilies shared similar exon-intron patterns and protein domain compositions, as well as conserved motifs and amino acid residues. The cis-regulatory elements related to SA were identified in the promoter regions of TaNPR1-like genes. The TaNPR1-like genes were intensively mapped on the chromosomes of homoeologous groups 3, 4, and 5, except TaNPR2-D. Chromosomal distribution and collinearity analysis of NPR1-like genes among bread wheat and its relatives revealed that the evolution of this gene family was more conservative following formation of hexaploid wheat. Transcriptome data analysis indicated that TaNPR1-like genes exhibited tissue/organ-specific expression patterns and some members were induced under biotic stress. These findings lay the foundation for further functional characterization of NPR1-like proteins in bread wheat and its relatives.

scholarly journals An atlas of wheat epigenetic regulatory elements reveals subgenome-divergence in the regulation of development and stress responses

2021 ◽  
Author(s):  
Meiyue Wang ◽  
Zijuan Li ◽  
Yu’e Zhang ◽  
Yuyun Zhang ◽  
Yilin Xie ◽  
...  
Keyword(s):  
Stress Responses ◽  
Affinity Purification ◽  
Regulatory Elements ◽  
Large Set ◽  
Transcriptional Responses ◽  
Polyploid Wheat ◽  
Temporal Regulation ◽  
Spatio Temporal ◽  
Cis And Trans ◽  
Epigenetic Signatures

Abstract Wheat (Triticum aestivum) has a large allohexaploid genome. Subgenome-divergent regulation contributed to genome plasticity and the domestication of polyploid wheat. However, the specificity encoded in the wheat genome determining subgenome-divergent spatio-temporal regulation has been largely unexplored. The considerable size and complexity of the genome are major obstacles to dissecting the regulatory specificity. Here, we compared the epigenomes and transcriptomes from a large set of samples under diverse developmental and environmental conditions. Thousands of distal epigenetic regulatory elements (distal-epiREs) were specifically linked to their target promoters with coordinated epigenomic changes. We revealed that subgenome-divergent activity of homologous regulatory elements are affected by specific epigenetic signatures. Subgenome-divergent epiRE regulation of tissue specificity is associated with dynamic modulation of H3K27me3 mediated by Polycomb complex and demethylases. Furthermore, quantitative epigenomic approaches detected key stress responsive cis- and trans-acting factors validated by DNA Affinity Purification and sequencing (DAP-seq), and demonstrated the coordinated interplay between epiRE sequence contexts, epigenetic factors, and transcription factors in regulating subgenome divergent transcriptional responses to external changes. Thus, this study provides a wealth of resources for elucidating the epiRE regulomics and subgenome-divergent regulation in hexaploid wheat, and gives new clues for interpreting genetic and epigenetic interplay in regulating the benefits of polyploid wheat.

scholarly journals Distal and proximal cis-regulatory elements sense X-chromosomal dosage and developmental state at the Xist locus

2021 ◽  
Author(s):  
Rutger A.F. Gjaltema ◽  
Till Schwämmle ◽  
Pauline Kautz ◽  
Michael Robson ◽  
Robert Schöpflin ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Embryonic Stem ◽  
Developmental State ◽  
Regulatory Elements ◽  
Developmental Time ◽  
Proximal Region ◽  
Spatial Proximity ◽  
Enhancer Activity ◽  
Regulatory Regions ◽  
Spatio Temporal

AbstractDevelopmental genes such as Xist, the master regulator of X-chromosome inactivation (XCI), are controlled by complex cis-regulatory landscapes, which decode multiple signals to establish specific spatio-temporal expression patterns. Xist integrates information on X-chromosomal dosage and developmental stage to trigger XCI at the primed pluripotent state in females only. Through a pooled CRISPR interference screen in differentiating mouse embryonic stem cells, we identify functional enhancer elements of Xist during the onset of random XCI. By quantifying how enhancer activity is modulated by X-dosage and differentiation, we find that X-dosage controls the promoter-proximal region in a binary switch-like manner. By contrast, differentiation cues activate a series of distal elements and bring them into closer spatial proximity of the Xist promoter. The strongest distal element is part of an enhancer cluster ∼200 kb upstream of the Xist gene which is associated with a previously unannotated Xist-enhancing regulatory transcript, we named Xert. Developmental cues and X-dosage are thus decoded by distinct regulatory regions, which cooperate to ensure female-specific Xist upregulation at the correct developmental time. Our study is the first step to disentangle how multiple, functionally distinct regulatory regions interact to generate complex expression patterns in mammals.

scholarly journals HDAC9 structural variants disrupting TWIST1 transcriptional regulation lead to craniofacial and limb malformations

2021 ◽  
Author(s):  
Naama Hirsch ◽  
Idit Dahan ◽  
Eva Dhaene ◽  
Matan Avni ◽  
Sarah Vergult ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Structural Variants ◽  
Protein Coding ◽  
Coding Sequences ◽  
Coding Sequence ◽  
Shh Pathway ◽  
Essential Components ◽  
Ctcf Site

Structural variants (SVs) can affect protein-coding sequences as well as gene regulatory elements. However, SVs disrupting protein-coding sequences that also function as cis-regulatory elements remain largely uncharacterized. Here, we show that craniosynostosis patients with SVs containing the Histone deacetylase 9 (HDAC9) protein-coding sequence are associated with disruption of TWIST1 regulatory elements that reside within HDAC9 sequence. Based on SVs within the HDAC9-TWIST1 locus, we defined the 3' HDAC9 sequence (~500Kb) as a critical TWIST1 regulatory region, encompassing craniofacial TWIST1 enhancers and CTCF sites. Deletions of either Twist1 enhancers (eTw5-7Δ/Δ) or Ctcf site (CtcfΔ/Δ) within the Hdac9 protein-coding sequence in mice led to decreased Twist1 expression and altered anterior\posterior limb expression patterns of Shh pathway genes. This decreased Twist1 expression results in a smaller sized and asymmetric skull and polydactyly that resembles Twist1+/− mouse phenotype. Chromatin conformation analysis revealed that the Twist1 promoter region interacts with Hdac9 sequences that encompass Twist1 enhancers and a Ctcf site and that interactions depended on the presence of both regulatory regions. Finally, a large inversion of the entire Hdac9 sequence (Hdac9INV/+) in mice that does not disrupt Hdac9 expression but repositions Twist1 regulatory elements showed decreased Twist1 expression and led to a craniosynostosis-like phenotype and polydactyly. Thus, our study elucidated essential components of TWIST1 transcriptional machinery that reside within the HDAC9 sequence, suggesting that SVs, encompassing protein-coding sequence, such as HDAC9, could lead to a phenotype that is not attributed to its protein function but rather to a disruption of the transcriptional regulation of a nearby gene, such as TWIST1.

scholarly journals Genome-wide identification and characterization of Solanum tuberosum BiP genes reveals the role of the promoter architecture in BiP gene diversity

2020 ◽  
Author(s):  
Venura Herath ◽  
Mathieu Gayral ◽  
Nirakar Adhikari ◽  
Rita Miller ◽  
Jeanmarie Verchot
Keyword(s):  
Solanum Tuberosum ◽  
Gene Diversity ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Linear Distribution ◽  
Potato Genome ◽  
Unfolded Protein ◽  
Promoter Architecture ◽  
Spatio Temporal ◽  
The Unfolded Protein Response

AbstractThe endoplasmic reticulum (ER) immunoglobulin binding proteins (BiPs) are molecular chaperones involved in normal protein maturation and refolding malformed proteins through the unfolded protein response (UPR). Plants BiPs belong to a multi-gene family contributing to development, immunity, and responses to environmental stresses. This study identified three BiP homologues in the Solanum tuberosum (potato) genome using phylogenetic, amino acid sequence, 3-D protein modeling and gene structure analysis. These analyses revealed that StBiP1 and StBiP2 grouped with AtBiP2, whereas StBiP3 grouped with AtBiP3. While the protein sequences and folding structures are highly similar, these StBiPs are distinguishable by their expression patterns in different tissues and in response to environmental stressors such as treatment with heat, chemicals, or virus elicitors of UPR. Ab initio promoter analysis revealed that potato and Arabidopsis BiP1 and BiP2 promoters were highly enriched with cis regulatory elements (CREs) linked to developmental processes, whereas BiP3 promoters were enriched with stress-related CREs. The frequency and linear distribution of these CREs produced two phylogenetic branches that further resolve the groups identified through gene phylogeny and exon/intron phase analysis. These data reveal that the CRE architecture of BiP promoters potentially define their spatio -temporal expression patterns under developmental and stress related cues.

scholarly journals Genome-Wide Analysis of the Homeobox Gene Family and Identification of Drought-Responsive Members in Populus trichocarpa

Plants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2284
Author(s):  
Jing Hou ◽  
Yan Sun ◽  
Lei Wang ◽  
Yuanzhong Jiang ◽  
Ningning Chen ◽  
...  
Keyword(s):  
Populus Trichocarpa ◽  
Expression Patterns ◽  
Dominant Gene ◽  
Homeobox Gene ◽  
Regulatory Elements ◽  
Virus Induced Gene Silencing ◽  
Motif Analysis ◽  
Significant Information ◽  
Spatio Temporal ◽  
Poplar Seedlings

Homeobox (HB) genes play critical roles in the regulation of plant morphogenesis, growth and development. Here, we identified a total of 156 PtrHB genes from the Populus trichocarpa genome. According to the topologies and taxonomy of the phylogenetic tree constructed by Arabidopsis thaliana HB members, all PtrHB proteins were divided into six subgroups, namely HD-ZIP, ZF-HD, HB-PHD, TALE, WOX and HB-OTHERS. Multiple alignments of conserved homeodomains (HDs) revealed the conserved loci of each subgroup, while gene structure analysis showed similar exon–intron gene structures, and motif analysis indicated the similarity of motif number and pattern in the same subgroup. Promoter analysis indicated that the promoters of PtrHB genes contain a series of cis-acting regulatory elements involved in responding to various abiotic stresses, indicating that PtrHBs had potential functions in these processes. Collinearity analysis revealed that there are 96 pairs of 127 PtrHB genes mainly distributing on Chromosomes 1, 2, and 5. We analyzed the spatio-temporal expression patterns of PtrHB genes, and the virus-induced gene silencing (VIGS) of PtrHB3 gene resulted in the compromised tolerance of poplar seedlings to mannitol treatment. The bioinformatics on PtrHB family and preliminary exploration of drought-responsive genes can provide support for further study of the family in woody plants, especially in drought-related biological processes. It also provides a direction for developing new varieties of poplar with drought resistance. Overall, our results provided significant information for further functional analysis of PtrHB genes in poplar and demonstrated that PtrHB3 is a dominant gene regulating tolerance to water stress treatment in poplar seedlings.

scholarly journals Spatio-temporal expression of phytoglobin: a determining factor in the NO specification of cell fate

2019 ◽  
Vol 70 (17) ◽  
pp. 4365-4377 ◽  
Author(s):  
Claudio Stasolla ◽  
Shuanglong Huang ◽  
Robert D Hill ◽  
Abir U Igamberdiev
Keyword(s):  
Cell Fate ◽  
Growth And Development ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Cell Behavior ◽  
Cell Tissue ◽  
Organ Specific ◽  
Response To Stress ◽  
Spatio Temporal ◽  
Determining Factor

AbstractPlant growth and development rely on the orchestration of cell proliferation, differentiation, and ultimately death. After varying rounds of divisions, cells respond to positional cues by acquiring a specific fate and embarking upon distinct developmental pathways which might differ significantly from those of adjacent cells exposed to diverse cues. Differential cell behavior is most apparent in response to stress, when some cells might be more vulnerable than others to the same stress condition. This appears to be the case for stem cells which show abnormal features of differentiation and ultimately signs of deterioration at the onset of specific types of stress such as hypoxia and water deficit. A determining factor influencing cell behavior during growth and development, and cell response during conditions of stress is nitric oxide (NO), the level of which can be regulated by phytoglobins (Pgbs), known scavengers of NO. The modulation of NO by Pgbs can be cell, tissue, and/or organ specific, as revealed by the expression patterns of Pgbs dictated by the presence of distinct cis-regulatory elements in their promoters. This review discusses how the temporal and spatial Pgb expression pattern influences NO-mediated responses and ultimately cell fate acquisition in plant developmental processes.

Selection of new biological activities from random nucleotide sequences: evolutionary and practical considerations

Genome ◽  
1989 ◽  
Vol 31 (1) ◽  
pp. 112-117 ◽  
Author(s):  
Marshall S. Z. Horwitz ◽  
Dipak K. Dube ◽  
Lawrence A. Loeb
Keyword(s):  
Dna Sequences ◽  
Active Sites ◽  
Biological Activities ◽  
Regulatory Elements ◽  
Biologically Active ◽  
Protein Domain ◽  
Protein Coding ◽  
Coding Sequences ◽  
Future Success ◽  
Selection Of

Recent advances in the selection of biologically active DNA sequences from random populations are reviewed. Within the framework of evolution, forces are considered that have precluded the testing of all possible DNA sequences, purely with regard to their functionality as genetic regulatory elements or protein coding sequences. Examples are drawn from cassette mutagenesis of enzyme active sites, protein domain replacement by fusion with random genomic digests, and the selection of bacterial promoters from random DNA. Efforts to derive new activities are examined, and the likelihood of future success is evaluated.Key words: active DNA, nucleotide permutation, DNA evolution.

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