scholarly journals Chromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue

2021 ◽  
Vol 14 (8) ◽  
pp. 765
Author(s):  
Marcin Janowski ◽  
Małgorzata Milewska ◽  
Peyman Zare ◽  
Aleksandra Pękowska
Keyword(s):  
Gene Expression ◽  
Neurological Disorders ◽  
Genome Engineering ◽  
New Technologies ◽  
Expression Patterns ◽  
Clinical Practices ◽  
Modifying Factors ◽  
Functional Consequences ◽  
Altered Gene ◽  
Regulatory Dna

Neurological disorders (NDs) comprise a heterogeneous group of conditions that affect the function of the nervous system. Often incurable, NDs have profound and detrimental consequences on the affected individuals’ lives. NDs have complex etiologies but commonly feature altered gene expression and dysfunctions of the essential chromatin-modifying factors. Hence, compounds that target DNA and histone modification pathways, the so-called epidrugs, constitute promising tools to treat NDs. Yet, targeting the entire epigenome might reveal insufficient to modify a chosen gene expression or even unnecessary and detrimental to the patients’ health. New technologies hold a promise to expand the clinical toolkit in the fight against NDs. (Epi)genome engineering using designer nucleases, including CRISPR-Cas9 and TALENs, can potentially help restore the correct gene expression patterns by targeting a defined gene or pathway, both genetically and epigenetically, with minimal off-target activity. Here, we review the implication of epigenetic machinery in NDs. We outline syndromes caused by mutations in chromatin-modifying enzymes and discuss the functional consequences of mutations in regulatory DNA in NDs. We review the approaches that allow modifying the (epi)genome, including tools based on TALENs and CRISPR-Cas9 technologies, and we highlight how these new strategies could potentially change clinical practices in the treatment of NDs.

PrfA Led to Reduced Biofilm Formation and Contributed to Altered Gene Expression Patterns in Biofilm-Forming Listeria monocytogenes

2013 ◽  
Vol 67 (3) ◽  
pp. 372-378 ◽  
Author(s):  
Qin Luo ◽  
Junli Shang ◽  
Xiaoqin Feng ◽  
Xinxin Guo ◽  
Liang Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Listeria Monocytogenes ◽  
Biofilm Formation ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Altered Gene Expression ◽  
Altered Gene

Altered gene expression patterns in ART offspring

2004 ◽  
Vol 82 ◽  
pp. S292 ◽  
Author(s):  
H.J. Kang ◽  
Y. Katagiri ◽  
Q.V. Neri ◽  
R. Baergen ◽  
Z. Rosenwaks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Altered Gene Expression ◽  
Altered Gene

scholarly journals How long does the mRNA remains stable in untreated whole bovine blood?

2021 ◽  
Author(s):  
Rodrigo Giglioti ◽  
Bianca Tainá Azevedo ◽  
Henrique Nunes de Oliveira ◽  
Luciana Morita Katiki ◽  
Anibal Eugênio Vercesi Filho ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Bovine Blood ◽  
Rna Integrity ◽  
Expression Studies ◽  
Gene Expression Studies ◽  
Altered Gene ◽  
The Stability

Abstract Background: High quality and quantity of messenger RNA (mRNA) are required for accuracy of gene expression studies and other RNA-based downstream applications. Since RNA is considered a labile macromolecular prone to degradation, which may result in falsely altered gene expression patterns, several commercial stabilizing reagents have been developed aiming to keep RNA stable for long period. However, for studies involving large number of experimental samples, the high costs related to these specific reagents may constitute a barrier. Methods and Results: In this context the present study was designed aiming to evaluate the stability of mRNA in whole bovine blood collected in EDTA tubes during storage at common fridge (4°C). Whole blood samples were collected from six Holstein calves and submitted to RNA extraction in each different interval: immediately after blood sampling (< 2 h), at 1-day post-sampling (dps), 2 dps, 3 dps, 7 dps and 14dps intervals. RNA integrity and purity were evaluated, and RT-qPCR assays were run using seven different genes (B2M, ACTB, PPIA, GAPDH, YWHAZ, CD4 and IFN-γ) aiming to evaluate the presence of altered gene transcription during storage. All extracted RNA samples presented high purity, while optimal integrity and unaltered gene expression were observed in whole experimental group up to 3 days of storage.Conclusion: Bovine blood RNA remained stable in K3EDTA tubes for 3 days stored at common fridge and can be successfully and accurately used for gene expression studies.

scholarly journals The legacy of diploid progenitors in allopolyploid gene expression patterns

2014 ◽  
Vol 369 (1648) ◽  
pp. 20130354 ◽  
Author(s):  
Richard J. A. Buggs ◽  
Jonathan F. Wendel ◽  
Jeffrey J. Doyle ◽  
Douglas E. Soltis ◽  
Pamela S. Soltis ◽  
...  
Keyword(s):  
Gene Expression ◽  
New Technologies ◽  
Expression Patterns ◽  
Genome Structure ◽  
Diploid Species ◽  
Duplicate Gene ◽  
Plant Evolution ◽  
Appropriate Technology ◽  
Major Question ◽  
Duplicate Gene Expression

Allopolyploidization (hybridization and whole-genome duplication) is a common phenomenon in plant evolution with immediate saltational effects on genome structure and gene expression. New technologies have allowed rapid progress over the past decade in our understanding of the consequences of allopolyploidy. A major question, raised by early pioneer of this field Leslie Gottlieb, concerned the extent to which gene expression differences among duplicate genes present in an allopolyploid are a legacy of expression differences that were already present in the progenitor diploid species. Addressing this question necessitates phylogenetically well-understood natural study systems, appropriate technology, availability of genomic resources and a suitable analytical framework, including a sufficiently detailed and generally accepted terminology. Here, we review these requirements and illustrate their application to a natural study system that Gottlieb worked on and recommended for this purpose: recent allopolyploids of Tragopogon (Asteraceae). We reanalyse recent data from this system within the conceptual framework of parental legacies on duplicate gene expression in allopolyploids. On a broader level, we highlight the intellectual connection between Gottlieb's phrasing of this issue and the more contemporary framework of cis- versus trans- regulation of duplicate gene expression in allopolyploid plants.

scholarly journals Altered gene expression patterns in muscle ring finger 1 null mice during denervation- and dexamethasone-induced muscle atrophy

2013 ◽  
Vol 45 (23) ◽  
pp. 1168-1185 ◽  
Author(s):  
J. David Furlow ◽  
Monica L. Watson ◽  
David S. Waddell ◽  
Eric S. Neff ◽  
Leslie M. Baehr ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscle Atrophy ◽  
Intracellular Signaling ◽  
Expression Patterns ◽  
Ring Finger ◽  
Altered Gene Expression ◽  
Catabolic State ◽  
Altered Gene ◽  
Multiple Conditions

Muscle atrophy can result from inactivity or unloading on one hand or the induction of a catabolic state on the other. Muscle-specific ring finger 1 (MuRF1), a member of the tripartite motif family of E3 ubiquitin ligases, is an essential mediator of multiple conditions inducing muscle atrophy. While most studies have focused on the role of MuRF1 in protein degradation, the protein may have other roles in regulating skeletal muscle mass and metabolism. We therefore systematically evaluated the effect of MuRF1 on gene expression during denervation and dexamethasone-induced atrophy. We find that the lack of MuRF1 leads to few differences in control animals, but there were several significant differences in specific sets of genes upon denervation- and dexamethasone-induced atrophy. For example, during denervation, MuRF1 knockout mice showed delayed repression of metabolic and structural genes and blunted induction of genes associated with the neuromuscular junction. In the latter case, this pattern correlates with blunted HDAC4 and myogenin upregulation. Lack of MuRF1 caused fewer changes in the dexamethasone-induced atrophy program, but certain genes involved in fat metabolism and intracellular signaling were affected. Our results demonstrate a new role for MuRF1 in influencing gene expression in two important models of muscle atrophy.

Altered gene expression patterns in intrauterine growth restriction: Potential role of hypoxia

2007 ◽  
Vol 196 (1) ◽  
pp. 70.e1-70.e6 ◽  
Author(s):  
Cathal McCarthy ◽  
Finbarr E. Cotter ◽  
Suzanne McElwaine ◽  
Anne Twomey ◽  
Eoghan E. Mooney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intrauterine Growth Restriction ◽  
Potential Role ◽  
Expression Patterns ◽  
Growth Restriction ◽  
Gene Expression Patterns ◽  
Intrauterine Growth ◽  
Altered Gene Expression ◽  
Altered Gene

scholarly journals Complex Relationships between Chromatin Accessibility, Sequence Divergence, and Gene Expression in Arabidopsis thaliana

2017 ◽  
Vol 35 (4) ◽  
pp. 837-854 ◽  
Author(s):  
Cristina M Alexandre ◽  
James R Urton ◽  
Ken Jean-Baptiste ◽  
John Huddleston ◽  
Michael W Dorrity ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Sequence Variation ◽  
Expression Patterns ◽  
Sequence Divergence ◽  
Chromatin Accessibility ◽  
Regulatory Dna ◽  
Regulatory Sites

AbstractVariation in regulatory DNA is thought to drive phenotypic variation, evolution, and disease. Prior studies of regulatory DNA and transcription factors across animal species highlighted a fundamental conundrum: Transcription factor binding domains and cognate binding sites are conserved, while regulatory DNA sequences are not. It remains unclear how conserved transcription factors and dynamic regulatory sites produce conserved expression patterns across species. Here, we explore regulatory DNA variation and its functional consequences within Arabidopsis thaliana, using chromatin accessibility to delineate regulatory DNA genome-wide. Unlike in previous cross-species comparisons, the positional homology of regulatory DNA is maintained among A. thaliana ecotypes and less nucleotide divergence has occurred. Of the ∼50,000 regulatory sites in A. thaliana, we found that 15% varied in accessibility among ecotypes. Some of these accessibility differences were associated with extensive, previously unannotated sequence variation, encompassing many deletions and ancient hypervariable alleles. Unexpectedly, for the majority of such regulatory sites, nearby gene expression was unaffected. Nevertheless, regulatory sites with high levels of sequence variation and differential chromatin accessibility were the most likely to be associated with differential gene expression. Finally, and most surprising, we found that the vast majority of differentially accessible sites show no underlying sequence variation. We argue that these surprising results highlight the necessity to consider higher-order regulatory context in evaluating regulatory variation and predicting its phenotypic consequences.

scholarly journals Quantitative comparison of the anterior-posterior patterning system in the embryos of five Drosophila species

2018 ◽  
Author(s):  
Zeba Wunderlich ◽  
Charless C. Fowlkes ◽  
Kelly B. Eckenrode ◽  
Meghan D. J. Bragdon ◽  
Arash Abiri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Evolutionary Developmental Biology ◽  
Drosophila Virilis ◽  
Gene Expression Patterns ◽  
Data Sets ◽  
Developmental Gene ◽  
Regulatory Dna ◽  
Anterior Posterior

AbstractComplex spatiotemporal gene expression patterns direct the development of the fertilized egg into an adult animal. Comparisons across species show that, in spite of changes in the underlying regulatory DNA sequence, developmental programs can be maintained across millions of years of evolution. Reciprocally, changes in gene expression can be used to generate morphological novelty. Distinguishing between changes in regulatory DNA that lead to changes in gene expression and those that do not is therefore a central goal of evolutionary developmental biology. Quantitative, spatially-resolved measurements of developmental gene expression patterns play a crucial role in this goal, enabling the detection of subtle phenotypic differences between species and the development of computations models that link the sequence of regulatory DNA to expression patterns. Here we report the generation of two atlases of cellular resolution gene expression measurements for the primary anterior-posterior patterning genes in Drosophila simulans and Drosophila virilis. By combining these data sets with existing atlases for three other Drosophila species, we detect subtle differences in the gene expression patterns and dynamics driving the highly conserved axis patterning system and delineate inter-species differences in the embryonic morphology. These data sets will be a resource for future modeling studies of the evolution of developmental gene regulatory networks.

scholarly journals An optimized pipeline for parallel image-based quantification of gene expression and genotyping after in situ hybridization

2017 ◽  
Author(s):  
Tomasz Dobrzycki ◽  
Monika Krecsmarik ◽  
Florian Bonkhofer ◽  
Roger Patient ◽  
Rui Monteiro
Keyword(s):  
Gene Expression ◽  
Image Analysis ◽  
In Situ Hybridization ◽  
Quantitative Methods ◽  
Genome Engineering ◽  
Expression Patterns ◽  
Computer Based ◽  
Molecular Phenotypes ◽  
Mutant Lines

ABSTRACTAdvances in genome engineering have resulted in the generation of numerous zebrafish mutant lines. A commonly used method to assess gene expression in the mutants is in situ hybridization (ISH). Because the embryos can be distinguished by genotype after ISH, comparing gene expression between wild type and mutant siblings can be done blinded and in parallel. Such experimental design reduces the technical variation between samples and minimises the risk of bias. This approach, however, requires an efficient method of genomic DNA extraction from post-ISH fixed zebrafish samples to ascribe phenotype to genotype. Here we describe a method to obtain PCR-quality DNA from 95-100% of zebrafish embryos, suitable for genotyping after ISH. In addition, we provide an image analysis protocol for quantifying gene expression of ISH-probed embryos, adaptable for the analysis of different expression patterns. Finally, we show that intensity-based image analysis enables accurate representation of the variability of gene expression detected by ISH and that it can complement quantitative methods like qRT-PCR. By combining genotyping after ISH and computer-based image analysis, we have established a high-confidence, unbiased methodology to assign gene expression levels to specific genotypes, and applied it to the analysis of molecular phenotypes of newly generated lmo4a mutants.SUMMARY STATEMENTOur optimized protocol to genotype zebrafish mutant embryos after in situ hybridization and digitally quantify the in situ signal will help to standardize existing experimental designs and methods of analysis.

199 IN VITRO-DEVELOPED BOVINE BLASTOCYSTS ARE MARKED WITH ABERRANT HYPER- AND HYPO-METHYLATED GENOMIC REGIONS

2015 ◽  
Vol 27 (1) ◽  
pp. 190
Author(s):  
D. Salilew-Wondim ◽  
M. Hoelker ◽  
U. Besenfelder ◽  
V. Havlicek ◽  
F. Rings ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Patterns ◽  
Proximal Promoter ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Altered Gene ◽  
Genomic Regions

Most often, in vitro produced embryos display poor quality and altered gene expression patterns compared to their in vivo counterparts. Aberrant DNA methylation occurring during in vitro embryo development is believed to be one of the multifaceted factors which may cause altered gene expression and poor embryo quality. Here, we investigated the genome-wide DNA methylation patterns of in vitro derived embryos using the recently developed Bovine EmbryoGENE Methylation Platform (BEGMP) array (Shojaei Saadi et al. BMC Genomics 2014 15, 451. doi: 10.1186/1471-2164-15-451) to unravel the aberrantly methylated genomic region in in vitro developed embryos. For this, in vitro and in vivo produced blastocysts were produced and used for genome-wide DNA methylation analysis. In vitro blastocysts were produced from oocytes retrieved from ovaries collected from the local abattoir and matured, fertilized, and cultured in vitro using SOF media. The in vivo blastocysts were produced by superovulation and AI of Simmental heifers followed by uterine flushing. Genomic DNA (gDNA) was then isolated from four replicates (each 10 blastocysts) of in vivo and in vitro derived blastocysts using Allprep DNA/RNA micro kit (Qiagen, Valencia, CA, USA) and the gDNA was then fragmented using the MseI enzyme. Following this, MseLig21 and MseLig were ligated to the MseI-digested genomic fragments in the presence of Ligase enzyme. Methyl-sensitive enzymes, HpaII, AciI, and Hinp1I, were used to cleave unmethlayted genomic regions within the MseI-MseI region of the fragmented DNA. The gDNA was subjected to two rounds of ligation-mediated polymerase chain reaction (LM-PCR) amplification. After removal of the adapters, the amplified gDNA samples from in vivo or in vitro groups were labelled either Cy-3 or Cy-5 dyes in dye-swap design using ULS Fluorescent gDNA labelling kit (Kreatech Biotechnology BV, Amsterdam, The Netherlands). Hybridization was performed for 40 h at 65°C. Slides were scanned using Agilent's High-Resolution C Scanner (Agilent Technologies Inc., Santa Clara, CA, USA) and features were extracted with Agilent's Feature Extraction software (Agilent Technologies Inc.). The results have shown that from a total of 414 566 probes harboured by the BEGMP array, 248 453 and 253 147 probes were detected in in vitro and in vivo derived blastocysts, respectively. Data analysis using the linear modelling for microarray (LIMMA) package and R software (The R Project for Statistical Computing, Vienna, Austria) revealed a total of 3434 differentially methylated regions (DMRs; Fold change ≥1.5, P-value <0.05), of which 42 and 58% were hyper- and hypo-methylated, respectively, in in vitro derived blastocysts compared to their in vivo counterparts. The DMRs were found to be localised in the intronic, exonic, promoter, proximal promoter, and distal promoter, and some of the probes did not have nearby genes. In addition, 10.8% of the DMRs were found to be stretched in short, long, or intermediate CpG islands. Thus, this study demonstrated genome-wide dysregulation in the epigenome landscape of in vitro-derived embryos by the time they reach to the blastocysts stage.

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