Histone H3K9 methylation promotes formation of genome compartments inCaenorhabditis elegansvia chromosome compaction and perinuclear anchoring

Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explore mechanisms controlling genome compartment organization inCaenorhabditis elegansand investigate roles for compartments in regulating gene expression. Distal arms ofC. eleganschromosomes, which are enriched for heterochromatic histone modifications H3K9me1/me2/me3, interact with each other bothin cisandin trans,while interacting less frequently with central regions, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genesmet-2andset-25significantly impaired formation of inactive Arm and active Center compartments.cec-4mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: Perinuclear anchoring of chromosome arms via CEC-4 to promote theircisassociation, and an anchoring-independent mechanism that compacts individual chromosome arms. In bothmet-2 set-25andcec-4mutants, no dramatic changes in gene expression were found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene-expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X established by the dosage compensation condensin complex. Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels.

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Genome-Wide Expression and Alternative Splicing in Domesticated Sunflowers (Helianthus annuus L.) under Flooding Stress

Agronomy ◽

10.3390/agronomy11010092 ◽

2021 ◽

Vol 11 (1) ◽

pp. 92

Author(s):

Joon Seon Lee ◽

Lexuan Gao ◽

Laura Melissa Guzman ◽

Loren H. Rieseberg

Keyword(s):

Gene Expression ◽

Alternative Splicing ◽

Mixed Model ◽

Agricultural Land ◽

Alcohol Fermentation ◽

Expression Levels ◽

Flooding Stress ◽

Genome Wide ◽

And Control ◽

Gene Expression Levels

Approximately 10% of agricultural land is subject to periodic flooding, which reduces the growth, survivorship, and yield of most crops, reinforcing the need to understand and enhance flooding resistance in our crops. Here, we generated RNA-Seq data from leaf and root tissue of domesticated sunflower to explore differences in gene expression and alternative splicing (AS) between a resistant and susceptible cultivar under both flooding and control conditions and at three time points. Using a combination of mixed model and gene co-expression analyses, we were able to separate general responses of sunflower to flooding stress from those that contribute to the greater tolerance of the resistant line. Both cultivars responded to flooding stress by upregulating expression levels of known submergence responsive genes, such as alcohol dehydrogenases, and slowing metabolism-related activities. Differential AS reinforced expression differences, with reduced AS frequencies typically observed for genes with upregulated expression. Significant differences were found between the genotypes, including earlier and stronger upregulation of the alcohol fermentation pathway and a more rapid return to pre-flooding gene expression levels in the resistant genotype. Our results show how changes in the timing of gene expression following both the induction of flooding and release from flooding stress contribute to increased flooding tolerance.

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Natural variation in fecundity is correlated with species-wide levels of divergence in Caenorhabditis elegans

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab168 ◽

2021 ◽

Author(s):

Gaotian Zhang ◽

Jake D Mostad ◽

Erik C Andersen

Keyword(s):

Life History ◽

Caenorhabditis Elegans ◽

Life History Traits ◽

Life History Trait ◽

Selective Sweeps ◽

C Elegans ◽

Genome Wide ◽

Genetic Complexity ◽

Genomic Regions ◽

Global Population

Abstract Life history traits underlie the fitness of organisms and are under strong natural selection. A new mutation that positively impacts a life history trait will likely increase in frequency and become fixed in a population (e.g. a selective sweep). The identification of the beneficial alleles that underlie selective sweeps provides insights into the mechanisms that occurred during the evolution of a species. In the global population of Caenorhabditis elegans, we previously identified selective sweeps that have drastically reduced chromosomal-scale genetic diversity in the species. Here, we measured the fecundity of 121 wild C. elegans strains, including many recently isolated divergent strains from the Hawaiian islands and found that strains with larger swept genomic regions have significantly higher fecundity than strains without evidence of the recent selective sweeps. We used genome-wide association (GWA) mapping to identify three quantitative trait loci (QTL) underlying the fecundity variation. Additionally, we mapped previous fecundity data from wild C. elegans strains and C. elegans recombinant inbred advanced intercross lines that were grown in various conditions and detected eight QTL using GWA and linkage mappings. These QTL show the genetic complexity of fecundity across this species. Moreover, the haplotype structure in each GWA QTL region revealed correlations with recent selective sweeps in the C. elegans population. North American and European strains had significantly higher fecundity than most strains from Hawaii, a hypothesized origin of the C. elegans species, suggesting that beneficial alleles that caused increased fecundity could underlie the selective sweeps during the worldwide expansion of C. elegans.

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Genome-Wide Gene Expression Analysis in Response to Organophosphorus Pesticide Chlorpyrifos and Diazinon in C. elegans

PLoS ONE ◽

10.1371/journal.pone.0012145 ◽

2010 ◽

Vol 5 (8) ◽

pp. e12145 ◽

Cited By ~ 30

Author(s):

Ana Viñuela ◽

L. Basten Snoek ◽

Joost A. G. Riksen ◽

Jan E. Kammenga

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Organophosphorus Pesticide ◽

C Elegans ◽

Genome Wide ◽

Genome Wide Gene Expression

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Behavior-dependent cis regulation reveals genes and pathways associated with bower building in cichlid fishes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1810140115 ◽

2018 ◽

Vol 115 (47) ◽

pp. E11081-E11090 ◽

Cited By ~ 15

Author(s):

Ryan A. York ◽

Chinar Patil ◽

Kawther Abdilleh ◽

Zachary V. Johnson ◽

Matthew A. Conte ◽

...

Keyword(s):

Gene Expression ◽

Neural Plasticity ◽

Genetic Basis ◽

Specific Expression ◽

Preferential Expression ◽

Cichlid Fishes ◽

Brain Gene Expression ◽

Genome Wide ◽

Allele Specific ◽

Genomic Regions

Many behaviors are associated with heritable genetic variation [Kendler and Greenspan (2006) Am J Psychiatry 163:1683–1694]. Genetic mapping has revealed genomic regions or, in a few cases, specific genes explaining part of this variation [Bendesky and Bargmann (2011) Nat Rev Gen 12:809–820]. However, the genetic basis of behavioral evolution remains unclear. Here we investigate the evolution of an innate extended phenotype, bower building, among cichlid fishes of Lake Malawi. Males build bowers of two types, pits or castles, to attract females for mating. We performed comparative genome-wide analyses of 20 bower-building species and found that these phenotypes have evolved multiple times with thousands of genetic variants strongly associated with this behavior, suggesting a polygenic architecture. Remarkably, F1 hybrids of a pit-digging and a castle-building species perform sequential construction of first a pit and then a castle bower. Analysis of brain gene expression in these hybrids showed that genes near behavior-associated variants display behavior-dependent allele-specific expression with preferential expression of the pit-digging species allele during pit digging and of the castle-building species allele during castle building. These genes are highly enriched for functions related to neurodevelopment and neural plasticity. Our results suggest that natural behaviors are associated with complex genetic architectures that alter behavior via cis-regulatory differences whose effects on gene expression are specific to the behavior itself.

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H3 K79 dimethylation marks developmental activation of the β-globin gene but is reduced upon LCR-mediated high-level transcription

Blood ◽

10.1182/blood-2007-12-128983 ◽

2008 ◽

Vol 112 (2) ◽

pp. 406-414 ◽

Cited By ~ 11

Author(s):

Tomoyuki Sawado ◽

Jessica Halow ◽

Hogune Im ◽

Tobias Ragoczy ◽

Emery H. Bresnick ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Activation ◽

Globin Gene ◽

Erythroid Differentiation ◽

Genome Wide ◽

Activation Of Transcription ◽

High Level ◽

The Relationship ◽

Mutant Genes ◽

Gene Expression Levels

Abstract Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired β-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Δ locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the β-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and ΔLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the ΔLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with β-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level β-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.

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An unusual genomic position effect on Drosophila white gene expression: pairing dependence, interactions with zeste, and molecular analysis of revertants.

Genetics ◽

10.1093/genetics/130.1.125 ◽

1992 ◽

Vol 130 (1) ◽

pp. 125-138 ◽

Cited By ~ 2

Author(s):

T Hazelrigg ◽

S Petersen

Keyword(s):

Gene Expression ◽

Regulatory Element ◽

Position Effect ◽

Insertion Site ◽

White Gene ◽

Chromosome 2 ◽

Wild Type ◽

Gene Copies ◽

In Trans ◽

In Cis

Abstract The white gene in the AR4-24 P[white,rosy] insertion on chromosome 2 has a novel expression pattern, in which it is repressed in the dorsal half of the eye. X-ray mutagenesis led to the isolation of six revertants mapping to chromosome 2, which are wild type in a zeste+ background, and three extreme derivatives, in which white gene expression is repressed in ventral regions of the eye as well. By Southern blot analyses the breakpoints of five of the revertants and one of the extreme derivatives were mapped in the flanking DNA bordering each side of the AR4-24 insertion. The revertants show some dorsal repression of white in the presence of z1, and by this criterion each is only a partial revertant. The extreme derivatives act not only in cis, but also in trans to repress expression of AR4-24 and its various derivatives. We provide evidence that these trans effects are proximity-dependent effects, possibly mediated by pairing of gene copies, as they do not extend to copies of the white gene located elsewhere in the genome. We show that one extreme derivative, E1, is a small deletion spanning the insertion site at the 5' end of the white gene, and propose that the distance between a negative regulatory element in the 5' flanking DNA and the white promoter influences the degree of the repression.

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Intra- and inter-specific variations of gene expression levels in yeast are largely neutral

10.1101/089995 ◽

2016 ◽

Cited By ~ 1

Author(s):

Jian-Rong Yang ◽

Calum Maclean ◽

Chungoo Park ◽

Huabin Zhao ◽

Jianzhi Zhang

Keyword(s):

Gene Expression ◽

Genome Sequence ◽

Large Fraction ◽

General Role ◽

Expression Levels ◽

Genome Wide ◽

Sequence Variations ◽

Expression Evolution ◽

Molecular Phenotypes ◽

Gene Expression Levels

ABSTRACTIt is commonly, although not universally, accepted that most intra- and inter-specific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only ∼0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra- and inter-specific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution.

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Chromatin interaction aware gene regulatory modeling with graph attention networks

10.1101/2021.03.31.437978 ◽

2021 ◽

Author(s):

Alireza Karbalayghareh ◽

Merve Sahin ◽

Christina S Leslie

Keyword(s):

Gene Expression ◽

Deep Learning ◽

Chromatin Interaction ◽

Learning Approach ◽

Chromosome Conformation ◽

Attention Networks ◽

Current State ◽

Regulatory Impact ◽

Sequence Elements ◽

Gene Expression Levels

Linking distal enhancers to genes and modeling their impact on target gene expression are longstanding unresolved problems in regulatory genomics and critical for interpreting non-coding genetic variation. Here we present a new deep learning approach called GraphReg that exploits 3D interactions from chromosome conformation capture assays in order to predict gene expression from 1D epigenomic data or genomic DNA sequence. By using graph attention networks to exploit the connectivity of distal elements and promoters, GraphReg more faithfully models gene regulation and more accurately predicts gene expression levels than dilated convolutional neural networks (CNNs), the current state-of-the-art deep learning approach for this task. Feature attribution used with GraphReg accurately identifies functional enhancers of genes, as validated by CRISPRi-FlowFISH and TAP-seq assays, outperforming both CNNs and the recently proposed Activity-by-Contact model. GraphReg therefore represents an important advance in modeling the regulatory impact of epigenomic and sequence elements.

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