Abstract 2210: DNA methylation to identify non-coding gene regulatory regions in tumor samples

2015 ◽  
Author(s):  
Benjamin P. Berman
Keyword(s):  
Dna Methylation ◽  
Regulatory Regions ◽  
Gene Regulatory

scholarly journals Nucleosomes and DNA methylation shape meiotic DSB frequency in Arabidopsis transposons and gene regulatory regions

2017 ◽  
Author(s):  
Kyuha Choi ◽  
Xiaohui Zhao ◽  
Christophe Lambing ◽  
Charles J. Underwood ◽  
Thomas J. Hardcastle ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Genome Instability ◽  
Nucleosome Occupancy ◽  
Plant Genome ◽  
Gene Promoters ◽  
Regulatory Regions ◽  
Plant Genomes ◽  
Meiotic Dsbs ◽  
Gene Regulatory

AbstractMeiotic recombination initiates via DNA double strand breaks (DSBs) generated by SPO11 topoisomerase-like complexes. Recombination frequency varies extensively along eukaryotic chromosomes, with hotspots controlled by chromatin and DNA sequence. To map meiotic DSBs throughout a plant genome, we purified and sequenced Arabidopsis SPO11-1-oligonucleotides. DSB hotspots occurred in gene promoters, terminators and introns, driven by AT-sequence richness, which excludes nucleosomes and allows SPO11-1 access. A strong positive relationship was observed between SPO11-1 DSBs and final crossover levels. Euchromatic marks promote recombination in fungi and mammals, and consistently we observe H3K4me3 enrichment in proximity to DSB hotspots at gene 5’-ends. Repetitive transposons are thought to be recombination-silenced during meiosis, in order to prevent non-allelic interactions and genome instability. Unexpectedly, we found strong DSB hotspots in nucleosome-depleted Helitron/Pogo/Tc1/Mariner DNA transposons, whereas retrotransposons were coldspots. Hotspot transposons are enriched within gene regulatory regions and in proximity to immunity genes, suggesting a role as recombination-enhancers. As transposon mobility in plant genomes is restricted by DNA methylation, we used the met1 DNA methyltransferase mutant to investigate the role of heterochromatin on the DSB landscape. Epigenetic activation of transposon meiotic DSBs occurred in met1 mutants, coincident with reduced nucleosome occupancy, gain of transcription and H3K4me3. Increased met1 SPO11-1 DSBs occurred most strongly within centromeres and Gypsy and CACTA/EnSpm coldspot transposons. Together, our work reveals complex interactions between chromatin and meiotic DSBs within genes and transposons, with significance for the diversity and evolution of plant genomes.

scholarly journals Simplified MethylRAD Sequencing to Detect Changes in DNA Methylation at Enhancer Elements in Differentiating Embryonic Stem Cells

Epigenomes ◽  
2020 ◽  
Vol 4 (4) ◽  
pp. 24
Author(s):  
Debapriya Saha ◽  
Allison B. Norvil ◽  
Nadia A. Lanman ◽  
Humaira Gowher
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Bioinformatic Analysis ◽  
Analysis Tool ◽  
Regulatory Regions ◽  
Genome Wide ◽  
Gene Regulatory ◽  
Pluripotency Genes

Differential DNA methylation is characteristic of gene regulatory regions, such as enhancers, which mostly constitute low or intermediate CpG content in their DNA sequence. Consequently, quantification of changes in DNA methylation at these sites is challenging. Given that DNA methylation across most of the mammalian genome is maintained, the use of genome-wide bisulfite sequencing to measure fractional changes in DNA methylation at specific sites is an overexertion which is both expensive and cumbersome. Here, we developed a MethylRAD technique with an improved experimental plan and bioinformatic analysis tool to examine regional DNA methylation changes in embryonic stem cells (ESCs) during differentiation. The transcriptional silencing of pluripotency genes (PpGs) during ESC differentiation is accompanied by PpG enhancer (PpGe) silencing mediated by the demethylation of H3K4me1 by LSD1. Our MethylRAD data show that in the presence of LSD1 inhibitor, a significant fraction of LSD1-bound PpGe fails to gain DNA methylation. We further show that this effect is mostly observed in PpGes with low/intermediate CpG content. Underscoring the sensitivity and accuracy of MethylRAD sequencing, our study demonstrates that this method can detect small changes in DNA methylation in regulatory regions, including those with low/intermediate CpG content, thus asserting its use as a method of choice for diagnostic purposes.

scholarly journals Genome-Wide Profiling of PARP1 Reveals an Interplay with Gene Regulatory Regions and DNA Methylation

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135410 ◽  
Author(s):  
Narasimharao Nalabothula ◽  
Taha Al-jumaily ◽  
Abdallah M. Eteleeb ◽  
Robert M. Flight ◽  
Shao Xiaorong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Regulatory Regions ◽  
Genome Wide ◽  
Gene Regulatory

scholarly journals Nucleosomes and DNA methylation shape meiotic DSB frequency in Arabidopsis thaliana transposons and gene regulatory regions

2018 ◽  
Vol 28 (4) ◽  
pp. 532-546 ◽  
Author(s):  
Kyuha Choi ◽  
Xiaohui Zhao ◽  
Andrew J. Tock ◽  
Christophe Lambing ◽  
Charles J. Underwood ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Arabidopsis Thaliana ◽  
Regulatory Regions ◽  
Gene Regulatory

scholarly journals Evolution of regulatory networks associated with traits under selection in cichlids

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tarang K. Mehta ◽  
Christopher Koch ◽  
Will Nash ◽  
Sara A. Knaack ◽  
Padhmanand Sudhakar ◽  
...  
Keyword(s):  
Visual System ◽  
Regulatory Sequence ◽  
Potential Candidate ◽  
East African ◽  
Regulatory Regions ◽  
A Genome ◽  
Opsin Genes ◽  
East African Cichlids ◽  
Gene Regulatory ◽  
African Cichlids

Abstract Background Seminal studies of vertebrate protein evolution speculated that gene regulatory changes can drive anatomical innovations. However, very little is known about gene regulatory network (GRN) evolution associated with phenotypic effect across ecologically diverse species. Here we use a novel approach for comparative GRN analysis in vertebrate species to study GRN evolution in representative species of the most striking examples of adaptive radiations, the East African cichlids. We previously demonstrated how the explosive phenotypic diversification of East African cichlids can be attributed to diverse molecular mechanisms, including accelerated regulatory sequence evolution and gene expression divergence. Results To investigate these mechanisms across species at a genome-wide scale, we develop a novel computational pipeline that predicts regulators for co-extant and ancestral co-expression modules along a phylogeny, and candidate regulatory regions associated with traits under selection in cichlids. As a case study, we apply our approach to a well-studied adaptive trait—the visual system—for which we report striking cases of network rewiring for visual opsin genes, identify discrete regulatory variants, and investigate their association with cichlid visual system evolution. In regulatory regions of visual opsin genes, in vitro assays confirm that transcription factor binding site mutations disrupt regulatory edges across species and segregate according to lake species phylogeny and ecology, suggesting GRN rewiring in radiating cichlids. Conclusions Our approach reveals numerous novel potential candidate regulators and regulatory regions across cichlid genomes, including some novel and some previously reported associations to known adaptive evolutionary traits.

scholarly journals Prediction of genome-wide effects of single nucleotide variants on transcription factor binding

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sebastian Carrasco Pro ◽  
Katia Bulekova ◽  
Brian Gregor ◽  
Adam Labadorf ◽  
Juan Ignacio Fuxman Bass
Keyword(s):  
Binding Sites ◽  
Cancer Type ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Regulatory Regions ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Gene Regulatory ◽  
The Impact ◽  
The Relationship

Abstract Single nucleotide variants (SNVs) located in transcriptional regulatory regions can result in gene expression changes that lead to adaptive or detrimental phenotypic outcomes. Here, we predict gain or loss of binding sites for 741 transcription factors (TFs) across the human genome. We calculated ‘gainability’ and ‘disruptability’ scores for each TF that represent the likelihood of binding sites being created or disrupted, respectively. We found that functional cis-eQTL SNVs are more likely to alter TF binding sites than rare SNVs in the human population. In addition, we show that cancer somatic mutations have different effects on TF binding sites from different TF families on a cancer-type basis. Finally, we discuss the relationship between these results and cancer mutational signatures. Altogether, we provide a blueprint to study the impact of SNVs derived from genetic variation or disease association on TF binding to gene regulatory regions.

scholarly journals Novel susceptability loci for osteoarthritis of the hand: Variants in coding EN GENE regulatory regions

2015 ◽  
Vol 23 ◽  
pp. A196
Author(s):  
C.G. Boer ◽  
M. de Kruijf ◽  
L. Broer ◽  
A. Hofman ◽  
A.G. Uitterlinden ◽  
...  
Keyword(s):  
Regulatory Regions ◽  
Gene Regulatory

scholarly journals DNA Methylation of Regulatory Regions of Imprinted Genes at Birth and Its Relation to Infant Temperament

2016 ◽  
Vol 8 ◽  
pp. GEG.S40538 ◽  
Author(s):  
Bernard F. Fuemmeler ◽  
Chien-Ti Lee ◽  
Adelheid Soubry ◽  
Edwin S. Iversen ◽  
Zhiqing Huang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Smoking Status ◽  
Small Sample Size ◽  
Methylation Status ◽  
Small Sample ◽  
Infant Temperament ◽  
Imprinted Genes ◽  
Blood Leukocytes ◽  
Regulatory Regions ◽  
Size Limits

BACKGROUND DNA methylation of the differentially methylated regions (DMRs) of imprinted genes is relevant to neurodevelopment. METHODS DNA methylation status of the DMRs of nine imprinted genes in umbilical cord blood leukocytes was analyzed in relation to infant behaviors and temperament (n = 158). RESULTS MEG3 DMR levels were positively associated with internalizing ( β = 0.15, P = 0.044) and surgency ( β = 0.19, P = 0.018) behaviors, after adjusting for birth weight, gender, gestational age at birth, maternal age at delivery, race/ethnicity, education level, smoking status, parity, and a history of anxiety or depression. Higher methylation levels at the intergenic MEG3-IG methylation regions were associated with surgency ( β = 0.28, P = 0.0003) and PEG3 was positively related to externalizing ( β = 0.20, P = 0.01) and negative affectivity ( β = 0.18, P = 0.02). CONCLUSION While the small sample size limits inference, these pilot data support gene-specific associations between epigenetic differences in regulatory regions of imprinted domains at birth and later infant temperament.

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