scholarly journals A role for chromatin topology in imprinted domain regulation

2016 ◽  
Vol 94 (1) ◽  
pp. 43-55 ◽  
Author(s):  
William A. MacDonald ◽  
Saqib S. Sachani ◽  
Carlee R. White ◽  
Mellissa R.W. Mann

Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunmiao Jiang ◽  
Gongbo Lv ◽  
Jinxin Ge ◽  
Bin He ◽  
Zhe Zhang ◽  
...  

AbstractGATA transcription factors (TFs) are involved in the regulation of growth processes and various environmental stresses. Although GATA TFs involved in abiotic stress in plants and some fungi have been analyzed, information regarding GATA TFs in Aspergillusoryzae is extremely poor. In this study, we identified and functionally characterized seven GATA proteins from A.oryzae 3.042 genome, including a novel AoSnf5 GATA TF with 20-residue between the Cys-X2-Cys motifs which was found in Aspergillus GATA TFs for the first time. Phylogenetic analysis indicated that these seven A. oryzae GATA TFs could be classified into six subgroups. Analysis of conserved motifs demonstrated that Aspergillus GATA TFs with similar motif compositions clustered in one subgroup, suggesting that they might possess similar genetic functions, further confirming the accuracy of the phylogenetic relationship. Furthermore, the expression patterns of seven A.oryzae GATA TFs under temperature and salt stresses indicated that A. oryzae GATA TFs were mainly responsive to high temperature and high salt stress. The protein–protein interaction network of A.oryzae GATA TFs revealed certain potentially interacting proteins. The comprehensive analysis of A. oryzae GATA TFs will be beneficial for understanding their biological function and evolutionary features and provide an important starting point to further understand the role of GATA TFs in the regulation of distinct environmental conditions in A.oryzae.


Epigenomics ◽  
2021 ◽  
Author(s):  
Beatriz Garcia-Ruiz ◽  
Manuel Castro de Moura ◽  
Gerard Muntané ◽  
Lourdes Martorell ◽  
Elena Bosch ◽  
...  

Aim: To investigate DDR1 methylation in the brains of bipolar disorder (BD) patients and its association with DDR1 mRNA levels and comethylation with myelin genes. Materials & methods: Genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) corrected for glial composition and DDR1 gene expression analysis in the occipital cortices of individuals with BD (n = 15) and healthy controls (n = 15) were conducted. Results: DDR1 5-methylcytosine levels were increased and directly associated with DDR1b mRNA expression in the brains of BD patients. We also observed that DDR1 was comethylated with a group of myelin genes. Conclusion: DDR1 is hypermethylated in BD brain tissue and is associated with isoform expression. Additionally, DDR1 comethylation with myelin genes supports the role of this receptor in myelination.


2016 ◽  
Vol 371 (1688) ◽  
pp. 20150114 ◽  
Author(s):  
Nancy G. Forger

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.


2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Tao Li ◽  
Jihe Zhu ◽  
Fangming Deng ◽  
Weiguo Wu ◽  
Zhibing Zheng ◽  
...  

Myricetin has been reported as a promising chemopreventive compound with multiple biofunctions. To evaluate its influence on gene expressions in genome-wide set and further investigate its anti-inflammatory property, the present study performed Gene Ontology and Ingenuity Pathway Analysis (IPA) to describe the basic gene expression characteristics by myricetin treatment in HepG2 cells, confirmed its multi-biofunction by real-time fluorescent quantitative PCR (RT-qPCR), and further verified its anti-inflammatory property by Western blotting and bio-plex-based cytokines assay. The IPA data showed that 337 gene expressions (48% of the top molecules) are disturbed over 2-fold, and the most possible biofunctions of myricetin are the effect on “cardiovascular disease, metabolic disease, and lipid metabolism,” via regulation of 28 molecules with statistic score of 46. RT-qPCR data confirmed the accuracy of microarray data, and cytokines assay results indicated that 6 of the total 27 inflammatory cytokine secretions were significantly inhibited by myricetin pretreatment, including TNF-α, IFN-γ, IL-1α, IL-1β, IL-2, and IL-6. The present study is the first time to elucidate the multi-function of myricetin in genome-wide set by IPA analysis and verify its anti-inflammatory property by proteomics of cytokines assay. Therefore, these results enrich the comprehensive bioactivities of myricetin and reveal that myricetin has powerful anti-inflammatory property, which provides encouragement for in vivo studies to verify its possible health benefits.


2009 ◽  
Vol 77 (5) ◽  
pp. 2113-2124 ◽  
Author(s):  
Juliane Ollinger ◽  
Barbara Bowen ◽  
Martin Wiedmann ◽  
Kathryn J. Boor ◽  
Teresa M. Bergholz

ABSTRACT Listeria monocytogenes σB and positive regulatory factor A (PrfA) are pleiotropic transcriptional regulators that coregulate a subset of virulence genes. A positive regulatory role for σB in prfA transcription has been well established; therefore, observations of increased virulence gene expression and hemolytic activity in a ΔsigB strain initially appeared paradoxical. To test the hypothesis that L. monocytogenes σB contributes to a regulatory network critical for appropriate repression as well as induction of virulence gene expression, genome-wide transcript profiling and follow-up quantitative reverse transcriptase PCR (qRT-PCR), reporter fusion, and phenotypic experiments were conducted using L. monocytogenes prfA*, prfA* ΔsigB, ΔprfA, and ΔprfA ΔsigB strains. Genome-wide transcript profiling and qRT-PCR showed that in the presence of active PrfA (PrfA*), σB is responsible for reduced expression of the PrfA regulon. σB-dependent modulation of PrfA regulon expression reduced the cytotoxic effects of a PrfA* strain in HepG2 cells, highlighting the functional importance of regulatory interactions between PrfA and σB. The emerging model of the role of σB in regulating overall PrfA activity includes a switch from transcriptional activation at the P2 prfA promoter (e.g., in extracellular bacteria when PrfA activity is low) to posttranscriptional downregulation of PrfA regulon expression (e.g., in intracellular bacteria when PrfA activity is high).


BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Jessica Brunquell ◽  
Stephanie Morris ◽  
Yin Lu ◽  
Feng Cheng ◽  
Sandy D. Westerheide

2001 ◽  
Vol 183 (24) ◽  
pp. 7329-7340 ◽  
Author(s):  
Robert Caldwell ◽  
Ron Sapolsky ◽  
Walter Weyler ◽  
Randal R. Maile ◽  
Stuart C. Causey ◽  
...  

ABSTRACT The availability of the complete sequence of the Bacillus subtilis chromosome (F. Kunst et al., Nature 390:249–256, 1997) makes possible the construction of genome-wide DNA arrays and the study of this organism on a global scale. Because we have a long-standing interest in the effects of scoC on late-stage developmental phenomena as they relate toaprE expression, we studied the genome-wide effects of ascoC null mutant with the goal of furthering the understanding of the role of scoC in growth and developmental processes. In the present work we compared the expression patterns of isogenic B. subtilis strains, one of which carries a null mutation in the scoC locus (scoC4). The results obtained indicate thatscoC regulates, either directly or indirectly, the expression of at least 560 genes in the B. subtilisgenome. ScoC appeared to repress as well as activate gene expression. Changes in expression were observed in genes encoding transport and binding proteins, those involved in amino acid, carbohydrate, and nucleotide and/or nucleoside metabolism, and those associated with motility, sporulation, and adaptation to atypical conditions. Changes in gene expression were also observed for transcriptional regulators, along with sigma factors, regulatory phosphatases and kinases, and members of sensor regulator systems. In this report, we discuss some of the phenotypes associated with the scoCmutant in light of the transcriptome changes observed.


2015 ◽  
Vol 173 (2) ◽  
pp. 185-195 ◽  
Author(s):  
Masanori Murakami ◽  
Takanobu Yoshimoto ◽  
Kazuhiko Nakabayashi ◽  
Kyoichiro Tsuchiya ◽  
Isao Minami ◽  
...  

ObjectiveThe pathophysiology of aldosterone-producing adenomas (APA) has been investigated intensively through genetic and genomic approaches. However, the role of epigenetics in APA is not fully understood. In the present study, we explored the relationship between gene expression and DNA methylation status in APA.MethodsWe conducted an integrated analysis of transcriptome and methylome data of paired APA-adjacent adrenal gland (AAG) samples from the same patient. The adrenal specimens were obtained from seven Japanese patients with APA who underwent adrenalectomy. Gene expression and genome-wide CpG methylation profiles were obtained from RNA and DNA samples that were extracted from those seven paired tissues.ResultsMethylome analysis showed global CpG hypomethylation in APA relative to AAG. The integration of gene expression and methylation status showed that 34 genes were up-regulated with CpG hypomethylation in APA. Of these, three genes (CYP11B2, MC2R, and HPX) may be related to aldosterone production, and five genes (PRRX1, RAB38, FAP, GCNT2, and ASB4) are potentially involved in tumorigenesis.ConclusionThe present study is the first methylome analysis to compare APA with AAG in the same patients. Our integrated analysis of transcriptome and methylome revealed DNA hypomethylation in APA and identified several up-regulated genes with DNA hypomethylation that may be involved in aldosterone production and tumorigenesis.


2019 ◽  
Author(s):  
Long Xiao ◽  
Zhiguang Zhao ◽  
Fei He ◽  
Zhuo Du

ABSTRACTAn important capacity of genes is the rapid change of expression levels to cope with environment, known as expression plasticity. Elucidating the genomic mechanisms determining expression plasticity is critical for understanding the molecular basis of phenotypic plasticity, fitness, and adaptation. In this study, we systematically quantified genome-wide gene expression plasticity in four metazoan species by integrating changes of expression levels under a large number of genetic and environmental conditions. From this, we demonstrated that expression plasticity measures a distinct feature of gene expression that is orthogonal to other well-studies features including gene expression potential and tissue specificity/broadness. Expression plasticity is conserved across species with important physiological implications. The magnitude of expression plasticity is highly correlated with gene function and genes with high plasticity are implicated in disease susceptibility. Genome-wide analysis identified many conserved promoter cis-elements, trans-acting factors (such as CFCF), and gene body histone modifications (H3K36me3, H3K79me2, and H4K20me1) that are significantly associated with expression plasticity. Analysis of expression changes in perturbation experiments further validated a causal role of specific transcription factors and histone modifications. Collectively, this work reveals general properties, physiological implications, and multivariable regulation of gene expression plasticity in metazoans, extending the mechanistic understanding of gene regulation.


2017 ◽  
Author(s):  
Anne Lorant ◽  
Sarah Pedersen ◽  
Irene Holst ◽  
Matthew B. Hufford ◽  
Klaus Winter ◽  
...  

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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