scholarly journals Differential evolution in 3′UTRs leads to specific gene expression in Staphylococcus

2020 ◽  
Vol 48 (5) ◽  
pp. 2544-2563 ◽  
Author(s):  
Pilar Menendez-Gil ◽  
Carlos J Caballero ◽  
Arancha Catalan-Moreno ◽  
Naiara Irurzun ◽  
Inigo Barrio-Hernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Bacterial Species ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Species Differentiation ◽  
Orthologous Genes ◽  
Genome Wide ◽  
Sequence Variations ◽  
Species Specific

Abstract The evolution of gene expression regulation has contributed to species differentiation. The 3′ untranslated regions (3′UTRs) of mRNAs include regulatory elements that modulate gene expression; however, our knowledge of their implications in the divergence of bacterial species is currently limited. In this study, we performed genome-wide comparative analyses of mRNAs encoding orthologous proteins from the genus Staphylococcus and found that mRNA conservation was lost mostly downstream of the coding sequence (CDS), indicating the presence of high sequence diversity in the 3′UTRs of orthologous genes. Transcriptomic mapping of different staphylococcal species confirmed that 3′UTRs were also variable in length. We constructed chimeric mRNAs carrying the 3′UTR of orthologous genes and demonstrated that 3′UTR sequence variations affect protein production. This suggested that species-specific functional 3′UTRs might be specifically selected during evolution. 3′UTR variations may occur through different processes, including gene rearrangements, local nucleotide changes, and the transposition of insertion sequences. By extending the conservation analyses to specific 3′UTRs, as well as the entire set of Escherichia coli and Bacillus subtilis mRNAs, we showed that 3′UTR variability is widespread in bacteria. In summary, our work unveils an evolutionary bias within 3′UTRs that results in species-specific non-coding sequences that may contribute to bacterial diversity.

scholarly journals Beyond the ENCODE project: using genomics and epigenomics strategies to study enhancer evolution

2013 ◽  
Vol 368 (1632) ◽  
pp. 20130022 ◽  
Author(s):  
Noboru Jo Sakabe ◽  
Marcelo A. Nobrega
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Dna Interaction ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Genome Wide ◽  
Identify Transcription Factor ◽  
Specific Proteins ◽  
Species Specific

The complex expression patterns observed for many genes are often regulated by distal transcription enhancers. Changes in the nucleotide sequences of enhancers may therefore lead to changes in gene expression, representing a central mechanism by which organisms evolve. With the development of the experimental technique of chromatin immunoprecipitation (ChIP), in which discrete regions of the genome bound by specific proteins can be identified, it is now possible to identify transcription factor binding events (putative cis -regulatory elements) in entire genomes. Comparing protein–DNA binding maps allows us, for the first time, to attempt to identify regulatory differences and infer global patterns of change in gene expression across species. Here, we review studies that used genome-wide ChIP to study the evolution of enhancers. The trend is one of high divergence of cis -regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. We speculate on the meaning of the differences observed and discuss that although ChIP experiments identify the biochemical event of protein–DNA interaction, it cannot determine whether the event results in a biological function, and therefore more studies are required to establish the effect of divergence of binding events on species-specific gene expression.

scholarly journals mtDNA eQTLs and the m1A 16S rRNA modification explain mtDNA tissue-specific gene expression pattern in humans

2018 ◽  
Author(s):  
Tal Cohen ◽  
Chen Mordechai ◽  
Alal Eran ◽  
Dan Mishmar
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
16S Rrna ◽  
Gene Expression Pattern ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Dependent Manner ◽  
Rna Seq ◽  
Genome Wide ◽  
The Impact

Expression quantitative trait loci (eQTLs) are instrumental in genome-wide identification of regulatory elements, yet were overlooked in the mitochondrial DNA (mtDNA). By analyzing 5079 RNA-seq samples from 23 tissues we identified association of ancient mtDNA SNPs (haplogroups T2, L2, J2 and V) and recurrent SNPs (mtDNA positions 263, 750, 1438 and 10398) with tissue-dependent mtDNA gene-expression. Since the recurrent SNPs independently occurred in different mtDNA genetic backgrounds, they constitute the best candidates to be causal eQTLs. Secondly, the discovery of mtDNA eQTLs in both coding and non-coding mtDNA regions, propose the identification of novel mtDNA regulatory elements. Third, we identified association between low m1A 947 MT-RNR2 (16S) rRNA modification levels and altered mtDNA gene-expression in twelve tissues. Such association disappeared in skin which was exposed to sun, as compared to sun-unexposed skin from the same individuals, thus supporting the impact of UV on mtDNA gene expression. Taken together, our findings reveal that both mtDNA SNPs and mt-rRNA modification affect mtDNA gene expression in a tissue-dependent manner.

scholarly journals Dynamic Interactions of Transcription Factors and Enhancer Reprogramming in Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Emily Zboril ◽  
Hannah Yoo ◽  
Lizhen Chen ◽  
Zhijie Liu
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Therapy Resistance ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Dynamic Interactions ◽  
Genome Wide ◽  
Dna Regulatory Elements

While improved tumor treatment has significantly reduced the overall mortality rates, invasive progression including recurrence, therapy resistance and metastasis contributes to the majority of deaths caused by cancer. Enhancers are essential distal DNA regulatory elements that control temporal- or spatial-specific gene expression patterns during development and other biological processes. Genome-wide sequencing has revealed frequent alterations of enhancers in cancers and reprogramming of distal enhancers has emerged as one of the important features for tumors. In this review, we will discuss tumor progression-associated enhancer dynamics, its transcription factor (TF) drivers and how enhancer reprogramming modulates gene expression during cancer invasive progression. Additionally, we will explore recent advancements in contemporary technology including single-cell sequencing, spatial transcriptomics and CUT&RUN, which have permitted integrated studies of enhancer reprogramming in vivo. Given the essential roles of enhancer dynamics and its drivers in controlling cancer progression and treatment outcome, understanding these changes will be paramount in mitigating invasive events and discovering novel therapeutic targets.

scholarly journals Genome-Wide Histone Modifications and CTCF Enrichment Predict Gene Expression in Sheep Macrophages

2021 ◽  
Vol 11 ◽  
Author(s):  
Alisha T. Massa ◽  
Michelle R. Mousel ◽  
Maria K. Herndon ◽  
David R. Herndon ◽  
Brenda M. Murdoch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Alveolar Macrophages ◽  
Immune Cell ◽  
Regulatory Elements ◽  
Chromatin Domain ◽  
Specific Gene ◽  
Topological Domains ◽  
Tissue Specific ◽  
Genome Wide

Alveolar macrophages function in innate and adaptive immunity, wound healing, and homeostasis in the lungs dependent on tissue-specific gene expression under epigenetic regulation. The functional diversity of tissue resident macrophages, despite their common myeloid lineage, highlights the need to study tissue-specific regulatory elements that control gene expression. Increasing evidence supports the hypothesis that subtle genetic changes alter sheep macrophage response to important production pathogens and zoonoses, for example, viruses like small ruminant lentiviruses and bacteria like Coxiella burnetii. Annotation of transcriptional regulatory elements will aid researchers in identifying genetic mutations of immunological consequence. Here we report the first genome-wide survey of regulatory elements in any sheep immune cell, utilizing alveolar macrophages. We assayed histone modifications and CTCF enrichment by chromatin immunoprecipitation with deep sequencing (ChIP-seq) in two sheep to determine cis-regulatory DNA elements and chromatin domain boundaries that control immunity-related gene expression. Histone modifications included H3K4me3 (denoting active promoters), H3K27ac (active enhancers), H3K4me1 (primed and distal enhancers), and H3K27me3 (broad silencers). In total, we identified 248,674 reproducible regulatory elements, which allowed assignment of putative biological function in macrophages to 12% of the sheep genome. Data exceeded the FAANG and ENCODE standards of 20 million and 45 million useable fragments for narrow and broad marks, respectively. Active elements showed consensus with RNA-seq data and were predictive of gene expression in alveolar macrophages from the publicly available Sheep Gene Expression Atlas. Silencer elements were not enriched for expressed genes, but rather for repressed developmental genes. CTCF enrichment enabled identification of 11,000 chromatin domains with mean size of 258 kb. To our knowledge, this is the first report to use immunoprecipitated CTCF to determine putative topological domains in sheep immune cells. Furthermore, these data will empower phenotype-associated mutation discovery since most causal variants are within regulatory elements.

scholarly journals The regulatory genome of the malaria vector Anopheles gambiae: integrating chromatin accessibility and gene expression

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
José L Ruiz ◽  
Lisa C Ranford-Cartwright ◽  
Elena Gómez-Díaz
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Anopheles Gambiae ◽  
Mosquito Control ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Malaria Vectors ◽  
Specific Gene ◽  
Mosquito Vector ◽  
Human Malaria

Abstract Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about their mechanisms of transcriptional regulation. We profiled chromatin accessibility by the assay for transposase-accessible chromatin by sequencing (ATAC-seq) in laboratory-reared A. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data, we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue-specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that were annotated to mosquito immune-related genes. Not only is this study important for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but the information we produced also has great potential for developing new mosquito-control and anti-malaria strategies.

A Global Vista of the Epigenomic State of the Mouse Submandibular Gland

2021 ◽  
pp. 002203452110120
Author(s):  
C. Gluck ◽  
S. Min ◽  
A. Oyelakin ◽  
M. Che ◽  
E. Horeth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Submandibular Salivary Gland ◽  
Data Sets ◽  
Control Mechanisms ◽  
Chromatin Immunoprecipitation Sequencing

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.

Profile of a mammalian sperm receptor

Development ◽  
1990 ◽  
Vol 108 (1) ◽  
pp. 1-17 ◽  
Author(s):  
P.M. Wassarman
Keyword(s):  
Gene Expression ◽  
Zona Pellucida ◽  
Specific Gene ◽  
Mammalian Development ◽  
Unique Nature ◽  
Mammalian Fertilization ◽  
Species Specific ◽  
Available Information ◽  
Mammalian Eggs ◽  
Sperm Receptor

Complementary molecules on the surface of eggs and sperm are responsible for species-specific interactions between gametes during fertilization in both plants and animals. In this essay, several aspects of current research on the mouse egg receptor for sperm, a zona pellucida glycoprotein called ZP3, are addressed. These include the structure, synthesis, and functions of the sperm receptor during oogenesis and fertilization in mice. Several conclusions are drawn from available information. These include (I) ZP3 is a member of a unique class of glycoproteins found exclusively in the extracellular coat (zona pellucida) of mammalian eggs. (II) ZP3 gene expression is an example of oocyte-specific and, therefore, sex-specific gene expression during mammalian development. (III) ZP3 is a structural glycoprotein involved in assembly of the egg extracellular coat during mammalian oogenesis. (IV) ZP3 is a sperm receptor involved in carbohydrate-mediated gamete recognition and adhesion during mammalian fertilization. (V) ZP3 is an inducer of sperm exocytosis (acrosome reaction) during mammalian fertilization. (VI) ZP3 participates in the secondary block to polyspermy following fertilization in mammals. (VII) The extracellular coat of other mammalian eggs contains a glycoprotein that is functionally analogous to mouse ZP3. The unique nature, highly restricted expression, and multiple roles of ZP3 during mammalian development make this glycoprotein a particularly attractive subject for investigation at both the cellular and molecular levels.

scholarly journals Genetic influences on cell type specific gene expression and splicing during neurogenesis elucidate regulatory mechanisms of brain traits

2020 ◽  
Author(s):  
Nil Aygün ◽  
Angela L. Elwell ◽  
Dan Liang ◽  
Michael J. Lafferty ◽  
Kerry E. Cheek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Risk Variants ◽  
Allele Specific ◽  
Cell Type Specific ◽  
Regulatory Effects

SummaryInterpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs and allele specific expression in primary human neural progenitors (n=85) and their sorted neuronal progeny (n=74). Using colocalization and TWAS, we uncover cell-type specific regulatory mechanisms underlying risk for these traits.

scholarly journals HCR-FlowFISH: A flexible CRISPR screening method to identify cis-regulatory elements and their target genes

2020 ◽  
Author(s):  
SK Reilly ◽  
SJ Gosai ◽  
A Gutierrez ◽  
JC Ulirsch ◽  
M Kanai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Screening Method ◽  
Cell Types ◽  
Regulatory Elements ◽  
Hybridization Chain Reaction ◽  
Genome Wide ◽  
Wide Range ◽  
Causal Variants ◽  
Endogenous Loci

AbstractCRISPR screens for cis-regulatory elements (CREs) have shown unprecedented power to endogenously characterize the non-coding genome. To characterize CREs we developed HCR-FlowFISH (Hybridization Chain Reaction Fluorescent In-Situ Hybridization coupled with Flow Cytometry), which directly quantifies native transcripts within their endogenous loci following CRISPR perturbations of regulatory elements, eliminating the need for restrictive phenotypic assays such as growth or transcript-tagging. HCR-FlowFISH accurately quantifies gene expression across a wide range of transcript levels and cell types. We also developed CASA (CRISPR Activity Screen Analysis), a hierarchical Bayesian model to identify and quantify CRE activity. Using >270,000 perturbations, we identified CREs for GATA1, HDAC6, ERP29, LMO2, MEF2C, CD164, NMU, FEN1 and the FADS gene cluster. Our methods detect subtle gene expression changes and identify CREs regulating multiple genes, sometimes at different magnitudes and directions. We demonstrate the power of HCR-FlowFISH to parse genome-wide association signals by nominating causal variants and target genes.

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