scholarly journals Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes

2020 ◽  
Vol 48 (8) ◽  
pp. 4115-4138 ◽  
Author(s):  
Marion Crespo ◽  
Annelaure Damont ◽  
Melina Blanco ◽  
Emmanuelle Lastrucci ◽  
Sara El Kennani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Integrated Analysis ◽  
Chromatin Binding ◽  
Dynamic Modification ◽  
Transcription Regulators ◽  
Level Of Understanding ◽  
Chemical Groups ◽  
Active Genes

Abstract Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.

scholarly journals Xrp1 genetically interacts with the ALS-associated FUS orthologue caz and mediates its toxicity

2018 ◽  
Vol 217 (11) ◽  
pp. 3947-3964 ◽  
Author(s):  
Moushami Mallik ◽  
Marica Catinozzi ◽  
Clemens B. Hug ◽  
Li Zhang ◽  
Marina Wagner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Life Span ◽  
Motor Neurons ◽  
Gene Expression Regulation ◽  
Genetic Interaction ◽  
Motor Deficits ◽  
Chromatin Binding ◽  
Mutant Phenotypes ◽  
Gene Expression Dysregulation ◽  
Lateral Sclerosis

Cabeza (caz) is the single Drosophila melanogaster orthologue of the human FET proteins FUS, TAF15, and EWSR1, which have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we identified Xrp1, a nuclear chromatin-binding protein, as a key modifier of caz mutant phenotypes. Xrp1 expression was strongly up-regulated in caz mutants, and Xrp1 heterozygosity rescued their motor defects and life span. Interestingly, selective neuronal Xrp1 knockdown was sufficient to rescue, and neuronal Xrp1 overexpression phenocopied caz mutant phenotypes. The caz/Xrp1 genetic interaction depended on the functionality of the AT-hook DNA-binding domain in Xrp1, and the majority of Xrp1-interacting proteins are involved in gene expression regulation. Consistently, caz mutants displayed gene expression dysregulation, which was mitigated by Xrp1 heterozygosity. Finally, Xrp1 knockdown substantially rescued the motor deficits and life span of flies expressing ALS mutant FUS in motor neurons, implicating gene expression dysregulation in ALS-FUS pathogenesis.

RNA Modifications in the Central Nervous System

2020 ◽  
Author(s):  
Dan Ohtan Wang
Keyword(s):  
Gene Expression ◽  
Cell Function ◽  
Gene Expression Regulation ◽  
Spinal Injury ◽  
Regulation Of Gene Expression ◽  
Modified Nucleosides ◽  
Rna Modifications ◽  
The Central Nervous System ◽  
Post Transcriptional Regulation ◽  
The Brain

Epitranscriptomics, a recently emerged field to investigate post-transcriptional regulation of gene expression through enzyme-mediated RNA modifications, is rapidly evolving and integrating with neuroscience. Using a rich repertoire of modified nucleosides and strategically positioning them to the functionally important and evolutionarily conserved regions of the RNA, epitranscriptomics dictates RNA-mediated cell function. The new field is quickly changing our view of the genetic geography in the brain during development and plasticity, impacting major functions from cortical neurogenesis, circadian rhythm, learning and memory, to reward, addiction, stress, stroke, and spinal injury, etc. Thus understanding the molecular components and operational rules of this pathway is becoming a key for us to decipher the genetic code for brain development, function, and disease. What RNA modifications are expressed in the brain? What RNAs carry them and rely on them for function? Are they dynamically regulated? How are they regulated and how do they contribute to gene expression regulation and brain function? This chapter summarizes recent advances that are beginning to answer these questions.

scholarly journals Roles of Transposable Elements in the Different Layers of Gene Expression Regulation

2019 ◽  
Vol 20 (22) ◽  
pp. 5755 ◽  
Author(s):  
Denise Drongitis ◽  
Francesco Aniello ◽  
Laura Fucci ◽  
Aldo Donizetti
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Chromatin Modification ◽  
Essential Element ◽  
Protein Translation ◽  
Expression Regulation ◽  
Molecular Processes ◽  
Eukaryotic Genomes

The biology of transposable elements (TEs) is a fascinating and complex field of investigation. TEs represent a substantial fraction of many eukaryotic genomes and can influence many aspects of DNA function that range from the evolution of genetic information to duplication, stability, and gene expression. Their ability to move inside the genome has been largely recognized as a double-edged sword, as both useful and deleterious effects can result. A fundamental role has been played by the evolution of the molecular processes needed to properly control the expression of TEs. Today, we are far removed from the original reductive vision of TEs as “junk DNA”, and are more convinced that TEs represent an essential element in the regulation of gene expression. In this review, we summarize some of the more recent findings, mainly in the animal kingdom, concerning the active roles that TEs play at every level of gene expression regulation, including chromatin modification, splicing, and protein translation.

Factor XIII-A is involved in the regulation of gene expression in alternatively activated human macrophages

2010 ◽  
Vol 104 (10) ◽  
pp. 709-717 ◽  
Author(s):  
Dániel Töröcsik ◽  
Lajos Széles ◽  
György Paragh ◽  
Zsuzsa Rákosy ◽  
Helga Bárdos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Factor Xiii ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Wound Response ◽  
Interleukin 4 ◽  
Alternative Activation ◽  
Wild Type ◽  
Functional Clustering ◽  
Alternatively Activated

SummaryFactor XIII subunit A (FXIII-A) is one of the most overrepresented genes that is expressed during the alternative activation of macrophages. Based on its substrate profile and its cellular localisation, FXIII-A is thought to function as an intracellular/intranuclear transglutaminase. Our aim was to find role for the intracellular FXIII-A by comparing the microarray profiles of alternatively activated monocyte-derived macrophages. Microarray analyses of FXIII-A-deficient patients and healthy controls were evaluated, followed by functional clustering of the differentially expressed genes. After a 48-hour differentiation in the presence of interleukin 4 (IL4), 1,017 probes out of the 24,398 expressed in macrophages from FXIII-A- deficient samples were IL4 sensitive, while only 596 probes were IL4 sensitive in wild-type samples. Of these genes, 307 were induced in both the deficient and the wild-type macrophages. Our results revealed that FXIII-A has important role(s) in mediating gene expression changes in macrophages during alternative activation. Functional clustering of the target genes carried out using Cytoscape/BiNGO and Ingenuity Pathways Analysis programs showed that, in the absence of FXIII-A, the most prominent differences are related to immune functions and to wound response. Our findings suggest that functional impairment of macrophages at the level of gene expression regulation plays a role in the wound healing defects of FXIII-A-deficient patients.

scholarly journals Using pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs

2018 ◽  
Author(s):  
Xiaofeng Xu ◽  
Haishuo Ji ◽  
Zhi Cheng ◽  
Xiufeng Jin ◽  
Xue Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Small Rnas ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Cost Effective ◽  
Rna Degradation ◽  
Point Of View ◽  
Rna Seq ◽  
Dsrna Cleavage

AbstractIn this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs. 5’ and 3’ sRNAs alone can be used to annotate mitochondrial with 1-bp resolution and nuclear non-coding genes and identify new steady-state RNAs, which are usually from functional genes. Using 5’, 3’ and intronic sRNAs, we revealed that the enzymatic dsRNA cleavage and RNAi could involve in the RNA degradation and gene expression regulation of U1 snRNA in human. The further study of 5’, 3’ and intronic sRNAs help rediscover double-stranded RNA (dsRNA) cleavage, RNA interference (RNAi) and the regulation of gene expression, which challenges the classical theories. In this study, we provided a simple and cost effective way for the annotation of mitochondrial and nuclear non-coding genes and the identification of new steady-state RNAs, particularly long non-coding RNAs (lncRNAs). We also provided a different point of view for cancer and virus, based on the new discoveries of dsRNA cleavage, RNAi and the regulation of gene expression.

scholarly journals Promoter Proximal Pausing Limits Tumorous Growth Induced by the Yki Transcription Factor in Drosophila

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Sanket Nagarkar ◽  
Ruchi Wasnik ◽  
Pravallika Govada ◽  
Stephen Cohen ◽  
L. S. Shashidhara
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Elongation Factor ◽  
Imaginal Discs ◽  
Link Type ◽  
Genome Wide ◽  
Wing Imaginal Discs ◽  
Tumorous Growth

Promoter proximal pausing (PPP) of RNA polymerase II has emerged as a crucial rate-limiting step in the regulation of gene expression. Regulation of PPP is brought about by complexes 7SK snRNP, P-TEFb (Cdk9/cycT), and the negative elongation factor (NELF), which are highly conserved from Drosophila to humans. Here, we show that RNAi-mediated depletion of bin3 or Hexim of the 7SK snRNP complex or depletion of individual components of the NELF complex enhances Yki-driven growth, leading to neoplastic transformation of Drosophila wing imaginal discs. We also show that increased CDK9 expression cooperates with Yki in driving neoplastic growth. Interestingly, overexpression of CDK9 on its own or in the background of depletion of one of the components of 7SK snRNP or the NELF complex necessarily, and specifically, needed Yki overexpression to cause tumorous growth. Genome-wide gene expression analyses suggested that deregulation of protein homeostasis is associated with tumorous growth of wing imaginal discs. As both Fat/Hippo/Yki pathway and PPP are highly conserved, our observations may provide insights into mechanisms of oncogenic function of YAP—the ortholog of Yki in humans.

scholarly journals The Role of lncRNAs in Gene Expression Regulation through mRNA Stabilization

2021 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Maialen Sebastian-delaCruz ◽  
Itziar Gonzalez-Moro ◽  
Ane Olazagoitia-Garmendia ◽  
Ainara Castellanos-Rubio ◽  
Izortze Santin
Keyword(s):  
Gene Expression ◽  
Mrna Stability ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Mrna Stabilization ◽  
Living Organisms ◽  
Almost All

mRNA stability influences gene expression and translation in almost all living organisms, and the levels of mRNA molecules in the cell are determined by a balance between production and decay. Maintaining an accurate balance is crucial for the correct function of a wide variety of biological processes and to maintain an appropriate cellular homeostasis. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of gene expression through different molecular mechanisms, including mRNA stabilization. In this review we provide an overview on the molecular mechanisms by which lncRNAs modulate mRNA stability and decay. We focus on how lncRNAs interact with RNA binding proteins and microRNAs to avoid mRNA degradation, and also on how lncRNAs modulate epitranscriptomic marks that directly impact on mRNA stability.

scholarly journals A description of the relationship in healthy longevity and aging-related disease: from gene to protein

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaolin Ni ◽  
Zhaoping Wang ◽  
Danni Gao ◽  
Huiping Yuan ◽  
Liang Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prolonged Exposure ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Human Longevity ◽  
Form Complex ◽  
Genetic Characteristics ◽  
Age Related ◽  
The Relationship

AbstractHuman longevity is a complex phenotype influenced by both genetic and environmental factors. It is also known to be associated with various types of age-related diseases, such as Alzheimer’s disease (AD) and cardiovascular disease (CVD). The central dogma of molecular biology demonstrates the conversion of DNA to RNA to the encoded protein. These proteins interact to form complex cell signaling pathways, which perform various biological functions. With prolonged exposure to the environment, the in vivo homeostasis adapts to the changes, and finally, humans adopt the phenotype of longevity or aging-related diseases. In this review, we focus on two different states: longevity and aging-related diseases, including CVD and AD, to discuss the relationship between genetic characteristics, including gene variation, the level of gene expression, regulation of gene expression, the level of protein expression, both genetic and environmental influences and homeostasis based on these phenotypes shown in organisms.

scholarly journals Epigenetic regulations through DNA methylation and hydroxymethylation: clues for early pregnancy in decidualization

2014 ◽  
Vol 5 (2) ◽  
pp. 95-107 ◽  
Author(s):  
Fei Gao ◽  
Sanjoy K. Das
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Fate ◽  
High Throughput Sequencing ◽  
Gene Expression Regulation ◽  
Epigenetic Modification ◽  
Regulation Of Gene Expression ◽  
Reproductive Organ ◽  
Epigenetic Changes ◽  
Dynamic Regulation

AbstractDNA methylation at cytosines is an important epigenetic modification that participates in gene expression regulation without changing the original DNA sequence. With the rapid progress of high-throughput sequencing techniques, whole-genome distribution of methylated cytosines and their regulatory mechanism have been revealed gradually. This has allowed the uncovering of the critical roles played by DNA methylation in the maintenance of cell pluripotency, determination of cell fate during development, and in diverse diseases. Recently, rediscovery of 5-hydroxymethylcytosine, and other types of modification on DNA, have uncovered more dynamic aspects of cell methylome regulation. The interaction of DNA methylation and other epigenetic changes remodel the chromatin structure and determine the state of gene transcription, not only permanently, but also transiently under certain stimuli. The uterus is a reproductive organ that experiences dramatic hormone stimulated changes during the estrous cycle and pregnancy, and thus provides us with a unique model for studying the dynamic regulation of epigenetic modifications. In this article, we review the current findings on the roles of genomic DNA methylation and hydroxymethylation in the regulation of gene expression, and discuss the progress of studies for these epigenetic changes in the uterus during implantation and decidualization.

scholarly journals The Regulatory Role of Histone Modification on Gene Expression in the Early Stage of Myocardial Infarction

2020 ◽  
Vol 7 ◽  
Author(s):  
Jinyu Wang ◽  
Bowen Lin ◽  
Yanping Zhang ◽  
Le Ni ◽  
Lingjie Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Histone Modifications ◽  
Gene Expression Regulation ◽  
Transcriptional Regulatory Network ◽  
Early Stage ◽  
Regulation Of Gene Expression ◽  
High Morbidity ◽  
Rna Seq ◽  
Histone Marks

Myocardial infarction (MI) is a fatal heart disease with high morbidity and mortality. Various studies have demonstrated that a series of relatively specific biological events occur within 24 h of MI. However, the roles of histone modifications in this pathological process are still poorly understood. To investigate the regulation of histone modifications on gene expression in early MI, we performed RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) on myocardial tissues 24 h after the onset of MI. The genome-wide profiles of five histone marks (H3K27ac, H3K9ac, H3K4me3, H3K9me3, and H3K27me3) were explored through ChIP-seq. RNA-seq identified 1,032 differentially expressed genes (DEGs) between the MI and sham groups. ChIP-seq analysis found that 195 upregulated DEGs were modified by change of at least one of the three active histone marks (H3K27ac, H3K9ac, and H3K4me3), and the biological processes and pathways analysis showed that these DEGs were significantly enriched in cardiomyocyte differentiation and development, inflammation, angiogenesis, and metabolism. In the transcriptional regulatory network, Ets1, Etv1, and Etv2 were predicted to be involved in gene expression regulation. In addition, by integrating super-enhancers (SEs) with RNA-seq data, 76 DEGs were associated with H3K27ac-enriched SEs in the MI group, and the functions of these SE-associated DEGs were mainly related to angiogenesis. Our results suggest that histone modifications may play important roles in the regulation of gene expression in the early stage of MI, and the early angiogenesis response may be initiated by SEs.

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