DNA methylation and control of genome organization in Neurospora crassa

Gene ◽  
1988 ◽  
Vol 74 (1) ◽  
pp. 109-111 ◽  
Author(s):  
Eric U. Selker ◽  
Edward B. Cambareri ◽  
Philip W. Garrett ◽  
Kenneth R. Haack ◽  
Bryan C. Jensen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Neurospora Crassa ◽  
Genome Organization ◽  
And Control

A targeted-replacement system for identification of signals for de novo methylation in Neurospora crassa

1994 ◽  
Vol 14 (11) ◽  
pp. 7059-7067
Author(s):  
V P Miao ◽  
M J Singer ◽  
M R Rountree ◽  
E U Selker
Keyword(s):  
Dna Methylation ◽  
Neurospora Crassa ◽  
De Novo ◽  
Gene Replacement ◽  
Position Effects ◽  
Efficient Gene ◽  
Bona Fide ◽  
Replacement System ◽  
Methylation Signal ◽  
De Novo Methylation

Transformation of eukaryotic cells can be used to test potential signals for DNA methylation. This approach is not always reliable, however, because of chromosomal position effects and because integration of multiple and/or rearranged copies of transforming DNA can influence DNA methylation. We developed a robust system to evaluate the potential of DNA fragments to function as signals for de novo methylation in Neurospora crassa. The requirements of the system were (i) a location in the N. crassa genome that becomes methylated only in the presence of a bona fide methylation signal and (ii) an efficient gene replacement protocol. We report here that the am locus fulfills these requirements, and we demonstrate its utility with the identification of a 2.7-kb fragment from the psi 63 locus as a new portable signal for de novo methylation.

A histone H3 methyltransferase controls DNA methylation in Neurospora crassa

Nature ◽  
2001 ◽  
Vol 414 (6861) ◽  
pp. 277-283 ◽  
Author(s):  
Hisashi Tamaru ◽  
Eric U. Selker
Keyword(s):  
Dna Methylation ◽  
Neurospora Crassa ◽  
Histone H3

scholarly journals Association between methylation in nasal epithelial TSLP gene and chronic rhinosinusitis with nasal polyps

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Jingyun Li ◽  
Jian Jiao ◽  
Yunbo Gao ◽  
Yuan Zhang ◽  
Luo Zhang
Keyword(s):  
Dna Methylation ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Inferior Turbinate ◽  
Nasal Resistance ◽  
Total Ige ◽  
Control Subjects ◽  
Human Nasal Epithelial Cells ◽  
Serum Total Ige ◽  
And Control

Abstract Background This study was performed to determine whether there was any association between abnormal DNA methylation of a thymic stromal lymphopoietin (TSLP) locus and pathogenesis of chronic rhinosinusitis (CRS). Methods A total of 48 CRS patients with nasal polyps (CRSwNP), 28 CRS patients without nasal polyps (CRSsNP) and 21 control subjects were enrolled into the study; and evaluated for serum total IgE level, olfactory score and nasal resistance. Samples were obtained from nasal polyps of CRSwNP patients, ethmoid mucosae of CRSsNP patients and inferior turbinate (IT) mucosa of control subjects during surgery, and used to isolate purified primary human nasal epithelial cells (HNECs). Genomic DNA was extracted from purified primary HNECs of each subject and DNA methylation ratios for a selected region of the TSLP gene were screened the using MassARRAY EpiTYPER. Results A total of 17 CpG units were analyzed; of which two CpG units (CpG3 and 22:23:24) had increased methylation ratios in the CRSwNP patients compared to the CRSsNP and control subjects after correction for false discovery rate (FDR) (Q < 0.1). The methylation ratios at both CpG3 and CpG22:23:24 units were positively correlated with olfactory score (r = 0.41, P = 0.0001; r = 0.25, P = 0.021) and unilateral nasal resistance at 75 Pa (r = 0.24, P = 0.04; r = 0.24, P = 0.036) and 150 Pa (r = 0.34, P = 0.004; r = 0.25, P = 0.031). Total nasal resistance at 75 Pa/150 Pa or serum total IgE levels were not correlated with the methylation ratios at either CpG unit. Conclusions Increased DNA methylation at the TSLP locus is likely to be associated with CRSwNP pathogenesis; however these findings need to be confirmed in larger multicentre group studies.

scholarly journals Experimental Parasite Infection Causes Genome-Wide Changes in DNA Methylation

2020 ◽  
Vol 37 (8) ◽  
pp. 2287-2299 ◽  
Author(s):  
Kostas Sagonas ◽  
Britta S Meyer ◽  
Joshka Kaufmann ◽  
Tobias L Lenz ◽  
Robert Häsler ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Infected Fish ◽  
Parasite Infection ◽  
Control Fish ◽  
Regulatory Processes ◽  
Neuropeptide Ff ◽  
Genome Wide ◽  
Parasite Infections ◽  
And Shifts ◽  
And Control

Abstract Parasites are arguably among the strongest drivers of natural selection, constraining hosts to evolve resistance and tolerance mechanisms. Although, the genetic basis of adaptation to parasite infection has been widely studied, little is known about how epigenetic changes contribute to parasite resistance and eventually, adaptation. Here, we investigated the role of host DNA methylation modifications to respond to parasite infections. In a controlled infection experiment, we used the three-spined stickleback fish, a model species for host–parasite studies, and their nematode parasite Camallanus lacustris. We showed that the levels of DNA methylation are higher in infected fish. Results furthermore suggest correlations between DNA methylation and shifts in key fitness and immune traits between infected and control fish, including respiratory burst and functional trans-generational traits such as the concentration of motile sperm. We revealed that genes associated with metabolic, developmental, and regulatory processes (cell death and apoptosis) were differentially methylated between infected and control fish. Interestingly, genes such as the neuropeptide FF receptor 2 and the integrin alpha 1 as well as molecular pathways including the Th1 and Th2 cell differentiation were hypermethylated in infected fish, suggesting parasite-mediated repression mechanisms of immune responses. Altogether, we demonstrate that parasite infection contributes to genome-wide DNA methylation modifications. Our study brings novel insights into the evolution of vertebrate immunity and suggests that epigenetic mechanisms are complementary to genetic responses against parasite-mediated selection.

scholarly journals Investigating skewness to understand gene expression heterogeneity in large patient cohorts

2019 ◽  
Vol 20 (S24) ◽  
Author(s):  
Benjamin V. Church ◽  
Henry T. Williams ◽  
Jessica C. Mar
Keyword(s):  
Dna Methylation ◽  
Methylation Status ◽  
Microarray Technology ◽  
Statistical Measure ◽  
Large Patient ◽  
Technology Platforms ◽  
Gene Expression Heterogeneity ◽  
Cancer Genome Atlas ◽  
Or Genes ◽  
And Control

Abstract Background Skewness is an under-utilized statistical measure that captures the degree of asymmetry in the distribution of any dataset. This study applied a new metric based on skewness to identify regulators or genes that have outlier expression in large patient cohorts. Results We investigated whether specific patterns of skewed expression were related to the enrichment of biological pathways or genomic properties like DNA methylation status. Our study used publicly available datasets that were generated using both RNA-sequencing and microarray technology platforms. For comparison, the datasets selected for this study also included different samples derived from control donors and cancer patients. When comparing the shift in expression skewness between cancer and control datasets, we observed an enrichment of pathways related to the immune function that reflects an increase towards positive skewness in the cancer relative to control datasets. A significant correlation was also detected between expression skewness and the top 500 genes corresponding to the most significant differential DNA methylation occurring in the promotor regions for four Cancer Genome Atlas cancer cohorts. Conclusions Our results indicate that expression skewness can reveal new insights into transcription based on outlier and asymmetrical behaviour in large patient cohorts.

scholarly journals Synthesis of Signals for De Novo DNA Methylation in Neurospora crassa

2003 ◽  
Vol 23 (7) ◽  
pp. 2379-2394 ◽  
Author(s):  
Hisashi Tamaru ◽  
Eric U. Selker
Keyword(s):  
Dna Methylation ◽  
Neurospora Crassa ◽  
Point Mutation ◽  
Dna Sequences ◽  
De Novo ◽  
Test Site ◽  
Minor Groove ◽  
Binding Motif ◽  
Repeat Induced Point Mutation

ABSTRACT Most 5-methylcytosine in Neurospora crassa occurs in A:T-rich sequences high in TpA dinucleotides, hallmarks of repeat-induced point mutation. To investigate how such sequences induce methylation, we developed a sensitive in vivo system. Tests of various 25- to 100-bp synthetic DNA sequences revealed that both T and A residues were required on a given strand to induce appreciable methylation. Segments composed of (TAAA) n or (TTAA) n were the most potent signals; 25-mers induced robust methylation at the special test site, and a 75-mer induced methylation elsewhere. G:C base pairs inhibited methylation, and cytosines 5′ of ApT dinucleotides were particularly inhibitory. Weak signals could be strengthened by extending their lengths. A:T tracts as short as two were found to cooperate to induce methylation. Distamycin, which, like the AT-hook DNA binding motif found in proteins such as mammalian HMG-I, binds to the minor groove of A:T-rich sequences, suppressed DNA methylation and gene silencing. We also found a correlation between the strength of methylation signals and their binding to an AT-hook protein (HMG-I) and to activities in a Neurospora extract. We propose that de novo DNA methylation in Neurospora cells is triggered by cooperative recognition of the minor groove of multiple short A:T tracts. Similarities between sequences subjected to repeat-induced point mutation in Neurospora crassa and A:T-rich repeated sequences in heterochromatin in other organisms suggest that related mechanisms control silent chromatin in fungi, plants, and animals.

scholarly journals LSD1 prevents aberrant heterochromatin formation in Neurospora crassa

2020 ◽  
Vol 48 (18) ◽  
pp. 10199-10210
Author(s):  
William K Storck ◽  
Vincent T Bicocca ◽  
Michael R Rountree ◽  
Shinji Honda ◽  
Tereza Ormsby ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Neurospora Crassa ◽  
Constitutive Heterochromatin ◽  
Histone H3 ◽  
Feedback Mechanism ◽  
Histone Demethylase ◽  
Histone Deacetylation ◽  
Heterochromatin Formation ◽  
Lysine Specific Demethylase ◽  
Specialized Form

Abstract Heterochromatin is a specialized form of chromatin that restricts access to DNA and inhibits genetic processes, including transcription and recombination. In Neurospora crassa, constitutive heterochromatin is characterized by trimethylation of lysine 9 on histone H3, hypoacetylation of histones, and DNA methylation. We explored whether the conserved histone demethylase, lysine-specific demethylase 1 (LSD1), regulates heterochromatin in Neurospora, and if so, how. Though LSD1 is implicated in heterochromatin regulation, its function is inconsistent across different systems; orthologs of LSD1 have been shown to either promote or antagonize heterochromatin expansion by removing H3K4me or H3K9me respectively. We identify three members of the Neurospora LSD complex (LSDC): LSD1, PHF1, and BDP-1. Strains deficient for any of these proteins exhibit variable spreading of heterochromatin and establishment of new heterochromatin domains throughout the genome. Although establishment of H3K9me3 is typically independent of DNA methylation in Neurospora, instances of DNA methylation-dependent H3K9me3 have been found outside regions of canonical heterochromatin. Consistent with this, the hyper-H3K9me3 phenotype of Δlsd1 strains is dependent on the presence of DNA methylation, as well as HCHC-mediated histone deacetylation, suggesting that spreading is dependent on some feedback mechanism. Altogether, our results suggest LSD1 works in opposition to HCHC to maintain proper heterochromatin boundaries.

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