Biphasic Chromatin Structure and FISH Signals Reflect Intranuclear Order

Background and Aim: One of the two parental allelic genes may selectively be expressed, regulated by imprinting, X-inactivation or by other less known mechanisms. This study aims to reflect on such genetic mechanisms. Materials and Methods: Slides from short term cultures or direct smears of blood, bone marrow and amniotic fluids were hybridized with FISH probes singly, combined or sequentially. Two to three hundred cells were examined from each preparation. Results and Aignificance: A small number of cells (up to about 5%), more frequent in leukemia cases, showed the twin features: (1) nuclei with biphasic chromatin, one part decondensed and the other condensed; and (2) homologous FISH signals distributed equitably in those two regions. The biphasic chromatin structure with equitable distribution of the homologous FISH signals may correspond to the two sets of chromosomes, supporting observations on ploidywise intranuclear order. The decondensed chromatin may relate to enhanced transcriptions or advanced replications. Conclusions: Transcriptions of only one of the two parental genomes cause allelic exclusion. Genomes may switch with alternating monoallelic expression of biallelic genes as an efficient genetic mechanism. If genomes fail to switch, allelic exclusion may lead to malignancy. Similarly, a genome-wide monoallelic replication may tilt the balance of heterozygosity resulting in aneusomy, initiating early events in malignant transformation and in predicting cancer mortality.

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Chromatin architectural proteins regulate flowering time by precluding gene looping

Science Advances ◽

10.1126/sciadv.abg3097 ◽

2021 ◽

Vol 7 (24) ◽

pp. eabg3097

Author(s):

Bo Zhao ◽

Yanpeng Xi ◽

Junghyun Kim ◽

Sibum Sung

Keyword(s):

Chromatin Structure ◽

Cellular Processes ◽

Genome Wide ◽

A Genome ◽

Evolutionarily Conserved ◽

Architectural Proteins ◽

Floral Repressor ◽

Flanking Regions ◽

Genome Wide Study

Chromatin structure is critical for gene expression and many other cellular processes. In Arabidopsis thaliana, the floral repressor FLC adopts a self-loop chromatin structure via bridging of its flanking regions. This local gene loop is necessary for active FLC expression. However, the molecular mechanism underlying the formation of this class of gene loops is unknown. Here, we report the characterization of a group of linker histone-like proteins, named the GH1-HMGA family in Arabidopsis, which act as chromatin architecture modulators. We demonstrate that these family members redundantly promote the floral transition through the repression of FLC. A genome-wide study revealed that this family preferentially binds to the 5′ and 3′ ends of gene bodies. The loss of this binding increases FLC expression by stabilizing the FLC 5′ to 3′ gene looping. Our study provides mechanistic insights into how a family of evolutionarily conserved proteins regulates the formation of local gene loops.

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Comparative transcriptome analysis of mule uncovered several heterosis-related genes for improving muscular endurance and cognition

10.1101/823047 ◽

2019 ◽

Author(s):

Shan Gao

Keyword(s):

Alternative Splicing ◽

Molecular Genetic ◽

Hybrid Vigor ◽

Neuronal System ◽

Future Studies ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms ◽

Productive Traits ◽

Genome Wide Gene Expression

AbstractHeterosis has been widely exploited in animal and plant breeding to enhance the productive traits of hybrid progeny of two breeds or two species. Although, there were multiple models for explaining the hybrid vigor, such as dominance and over-dominance hypothesis, its underlying molecular genetic mechanisms remain equivocal. The aim of this study is through comparing the different expression genes (DEGs) and different alternative splicing (DAS) genes to explore the mechanism of heterosis. Here, we performed a genome-wide gene expression and alternative splicing analysis of two heterotic crosses between donkey and horse in three tissues. The results showed that the DAS genes influenced the heterosis-related phenotypes in a unique than DEGs and about 10% DEGs are DAS genes. In addition, over 69.7% DEGs and 87.2% DAS genes showed over-dominance or dominance, respectively. Furthermore, the “Muscle Contraction” and “Neuronal System” pathways were significantly enriched both for the DEGs and DAS genes in muscle. TNNC2 and RYR1 genes may contribute to mule’s great endurance while GRIA2 and GRIN1 genes may be related with mule’s cognition. Together, these DEGs and DAS genes provide the candidates for future studies of the genetic and molecular mechanism of heterosis in mule.

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Tandem Directional CTCF Sites Balance Protocadherin Promoter Usage

10.1101/525543 ◽

2019 ◽

Cited By ~ 2

Author(s):

Qiang Wu ◽

Ya Guo ◽

Yujia Lu ◽

Jingwei Li ◽

Yonghu Wu ◽

...

Keyword(s):

Single Cells ◽

Computational Simulation ◽

Ctcf Binding ◽

Monoallelic Expression ◽

3D Genome ◽

Genome Wide ◽

A Genome ◽

Mammalian Genomes ◽

Wide Scale ◽

Promoter Usage

ABSTRACTCTCF is a key insulator-binding protein and mammalian genomes contain numerous CTCF-binding sites (CBSs), many of which are organized in tandem arrays. Here we provide direct evidence that CBSs, if located between enhancers and promoters in the Pcdhα and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation and experimental capture revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter usage. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.

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Identification of Genes Regulating Cell Death inStaphylococcus aureus

10.1101/569053 ◽

2019 ◽

Author(s):

Rebecca Yee ◽

Jie Feng ◽

Jiou Wang ◽

Jiazhen Chen ◽

Ying Zhang

Keyword(s):

Cell Death ◽

Acetic Acid ◽

Drug Targets ◽

Opportunistic Pathogen ◽

Infection Model ◽

Chronic Infections ◽

Bacterial Cell Death ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms

AbstractStaphylococcus aureusis an opportunistic pathogen that causes acute and chronic infections. Due toS. aureus’ s highly resistant and persistent nature, it is paramount to identify better drug targets in order to eradicateS. aureusinfections. Despite the efforts in understanding bacterial cell death, the genes and pathways ofS. aureuscell death remain elusive. Here, we performed a genome-wide screen using a transposon mutant library to study the genetic mechanisms involved inS. aureuscell death. Using a precisely controlled heat-ramp and acetic acid exposure assays, mutations in 27 core genes (hsdR1, hslO, nsaS, sspA, folD, mfd, vraF, kdpB, USA300HOU_2684, 0868, 0369, 0420, 1154, 0142, 0930, 2590, 0997, 2559, 0044, 2004, 1209, 0152, 2455, 0154, 2386, 0232, 0350 involved in transporters, transcription, metabolism, peptidases, kinases, transferases, SOS response, nucleic acid and protein synthesis) caused the bacteria to be more death-resistant. In addition, we identified mutations in core 10 genes (capA, gltT, mnhG1,USA300HOU_1780, 2496, 0200, 2029, 0336, 0329, 2386, involved in transporters, metabolism, transcription, cell wall synthesis) from heat-ramp and acetic acid that caused the bacteria to be more death-sensitive or with defect in persistence. Interestingly, death-resistant mutants were more virulent than the parental strain USA300 and caused increased mortality in aCaenorhabditis elegansinfection model. Conversely, death-sensitive mutants were less persistent and formed less persister cells upon exposure to different classes of antibiotics. These findings provide new insights into the mechanisms ofS. aureuscell death and offer new therapeutic targets for developing more effective treatments caused byS. aureus.

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The Potential Role of Genetic Assimilation during Maize Domestication

10.1101/105940 ◽

2017 ◽

Cited By ~ 2

Author(s):

Anne Lorant ◽

Sarah Pedersen ◽

Irene Holst ◽

Matthew B. Hufford ◽

Klaus Winter ◽

...

Keyword(s):

Gene Expression ◽

Zea Mays ◽

Potential Role ◽

Expression Patterns ◽

Genetic Assimilation ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms ◽

Maize Domestication

ABSTRACTDomestication research has largely focused on identification of morphological and genetic differences between extant populations of crops and their wild relatives. Little attention has been paid to the potential effects of environment despite substantial known changes in climate from the time of domestication to modern day. Recent research, in which maize and teosinte (i.e., wild maize) were exposed to environments similar to the time of domestication, resulted in a plastic induction of domesticated phenotypes in teosinte and little response to environment in maize. These results suggest that early agriculturalists may have selected for genetic mechanisms that cemented domestication phenotypes initially induced by a plastic response of teosinte to environment, a process known as genetic assimilation. To better understand this phenomenon and the potential role of environment in maize domestication, we examined differential gene expression in maize (Zea mays ssp. mays) and teosinte (Zea mays ssp. parviglumis) between past and present conditions. We identified a gene set of over 2000 loci showing a change in expression across environmental conditions in teosinte and invariance in maize. In fact, overall we observed both greater plasticity in gene expression and more substantial re-wiring of expression networks in teosinte across environments when compared to maize. While these results suggest genetic assimilation played at least some role in domestication, genes showing expression patterns consistent with assimilation are not significantly enriched for previously identified domestication candidates, indicating assimilation did not have a genome-wide effect.

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Genome-wide association study reveals the genetic determinism of growth traits in a Gushi-Anka F2 chicken population

Heredity ◽

10.1038/s41437-020-00365-x ◽

2020 ◽

Author(s):

Yanhua Zhang ◽

Yuzhe Wang ◽

Yiyi Li ◽

Junfeng Wu ◽

Xinlei Wang ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Growth Traits ◽

Carcass Traits ◽

Significant Snps ◽

Genome Wide Association ◽

Pathway Enrichment Analysis ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms

Abstract Chicken growth traits are economically important, but the relevant genetic mechanisms have not yet been elucidated. Herein, we performed a genome-wide association study to identify the variants associated with growth traits. In total, 860 chickens from a Gushi-Anka F2 resource population were phenotyped for 68 growth and carcass traits, and 768 samples were genotyped based on the genotyping-by-sequencing (GBS) method. Finally, 734 chickens and 321,314 SNPs remained after quality control and removal of the sex chromosomes, and these data were used to carry out a GWAS analysis. A total of 470 significant single-nucleotide polymorphisms (SNPs) for 43 of the 68 traits were detected and mapped on chromosomes (Chr) 1–6, -9, -10, -16, -18, -23, and -27. Of these, the significant SNPs in Chr1, -4, and -27 were found to be associated with more than 10 traits. Multiple traits shared significant SNPs, indicating that the same mutation in the region might have a large effect on multiple growth or carcass traits. Haplotype analysis revealed that SNPs within the candidate region of Chr1 presented a mosaic pattern. The significant SNPs and pathway enrichment analysis revealed that the MLNR, MED4, CAB39L, LDB2, and IGF2BP1 genes could be putative candidate genes for growth and carcass traits. The findings of this study improve our understanding of the genetic mechanisms regulating chicken growth and carcass traits and provide a theoretical basis for chicken breeding programs.

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Allelotyping of Follicular Thyroid Carcinoma: Frequent Allelic Losses in Chromosome Arms 7q, 11p, and 22q

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.9.7853 ◽

2001 ◽

Vol 86 (9) ◽

pp. 4268-4272 ◽

Cited By ~ 20

Author(s):

Yutaka Kitamura ◽

Kazuo Shimizu ◽

Koichi Ito ◽

Shigeo Tanaka ◽

Mitsuru Emi

Keyword(s):

Thyroid Carcinoma ◽

Follicular Thyroid Carcinoma ◽

Allelic Loss ◽

Mean Frequency ◽

Thyroid Carcinomas ◽

Real Frequency ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms ◽

The Mean

The genetic mechanisms involved in development of follicular thyroid carcinoma are poorly understood, although allelic losses (LOH) in this type of tumor have been reported in small panels of follicular thyroid carcinomas examined in earlier studies. To clarify the real frequency of allelic loss we carried out a genome-wide allelotyping study of 66 follicular thyroid carcinomas using 39 microsatellite markers representing all nonacrocentric autosomal arms. The mean frequency of LOH was 9.2%, and the mean fractional allelic loss was 0.09. The most frequent allelic losses were detected in 7q (28%), 11p (28%), and 22q (41%). When we compared these results with our previous allelotyping studies using identical markers in other types of thyroid cancers, the 9.2% mean frequency of allelic loss detected in follicular thyroid carcinomas was higher than that in papillary thyroid carcinomas (3%), but not as high as that detected in anaplastic thyroid carcinomas (20%). Frequent allelic losses of markers on chromosomes 7q, 11p, and 22q suggest locations to examine for the presence of suppressor genes associated with the development of follicular thyroid carcinoma.

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Identification of putative markers of triclabendazole resistance by a genome-wide analysis of genetically recombinant Fasciola hepatica

Parasitology ◽

10.1017/s0031182013000528 ◽

2013 ◽

Vol 140 (12) ◽

pp. 1523-1533 ◽

Cited By ~ 31

Author(s):

J. HODGKINSON ◽

K. CWIKLINSKI ◽

N. J. BEESLEY ◽

S. PATERSON ◽

D. J. L. WILLIAMS

Keyword(s):

Genetic Resources ◽

Fasciola Hepatica ◽

Genome Wide Analysis ◽

Extensive Analysis ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms ◽

Triclabendazole Resistance

SUMMARYDespite years of investigation into triclabendazole (TCBZ) resistance in Fasciola hepatica, the genetic mechanisms responsible remain unknown. Extensive analysis of multiple triclabendazole-susceptible and -resistant isolates using a combination of experimental in vivo and in vitro approaches has been carried out, yet few, if any, genes have been demonstrated experimentally to be associated with resistance phenotypes in the field. In this review we summarize the current understanding of TCBZ resistance from the approaches employed to date. We report the current genomic and genetic resources for F. hepatica that are available to facilitate novel functional genomics and genetic experiments for this parasite in the future. Finally, we describe our own non-biased approach to mapping the major genetic loci involved in conferring TCBZ resistance in F. hepatica.

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A genome-wide survey of human short-term memory

Molecular Psychiatry ◽

10.1038/mp.2009.133 ◽

2009 ◽

Vol 16 (2) ◽

pp. 184-192 ◽

Cited By ~ 25

Author(s):

A Papassotiropoulos ◽

K Henke ◽

E Stefanova ◽

A Aerni ◽

A Müller ◽

...

Keyword(s):

Short Term Memory ◽

Short Term ◽

Term Memory ◽

Genome Wide ◽

A Genome ◽

Genome Wide Survey

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DNA microarrays, a novel approach in studies of chromatin structure.

Acta Biochimica Polonica ◽

10.18388/abp.2004_3592 ◽

2004 ◽

Vol 51 (1) ◽

pp. 1-8

Author(s):

Piotr Widłak

Keyword(s):

Gene Expression ◽

Dna Microarray ◽

Chromatin Structure ◽

Expression Profiling ◽

Genetic Information ◽

Dna Microarrays ◽

Microarray Technology ◽

Genome Wide ◽

A Genome ◽

Wide Scale

The DNA microarray technology delivers an experimental tool that allows surveying expression of genetic information on a genome-wide scale at the level of single genes--for the new field termed functional genomics. Gene expression profiling--the primary application of DNA microarrays technology--generates monumental amounts of information concerning the functioning of genes, cells and organisms. However, the expression of genetic information is regulated by a number of factors that cannot be directly targeted by standard gene expression profiling. The genetic material of eukaryotic cells is packed into chromatin which provides the compaction and organization of DNA for replication, repair and recombination processes, and is the major epigenetic factor determining the expression of genetic information. Genomic DNA can be methylated and this modification modulates interactions with proteins which change the functional status of genes. Both chromatin structure and transcriptional activity are affected by the processes of replication, recombination and repair. Modified DNA microarray technology could be applied to genome-wide study of epigenetic factors and processes that modulate the expression of genetic information. Attempts to use DNA microarrays in studies of chromatin packing state, chromatin/DNA-binding protein distribution and DNA methylation pattern on a genome-wide scale are briefly reviewed in this paper.

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