scholarly journals Features of Methylation and Gene Expression in the Promoter-Associated CpG Islands Using Human Methylome Data

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Xin Du ◽  
Leng Han ◽  
An-Yuan Guo ◽  
Zhongming Zhao
Keyword(s):  
Gene Expression ◽  
Methylation Level ◽  
Cpg Island ◽  
Expression Patterns ◽  
Cpg Islands ◽  
Gc Content ◽  
Gene Markers ◽  
A Genome ◽  
Genome Level ◽  
Lower Ratio

CpG islands are typically located in the 5′end of genes and considered as gene markers because they play important roles in gene regulation via epigenetic change. In this study, we compared the features of CpG islands identified by several major algorithms by setting the parameter cutoff values in order to obtain a similar number of CpG islands in a genome. This approach allows us to systematically compare the methylation and gene expression patterns in the identified CpG islands. We found that Takai and Jones’ algorithm tends to identify longer CpG islands but with weaker CpG island features (e.g., lower GC content and lower ratio of the observed over expected CpGs) and higher methylation level. Conversely, the CpG clusters identified by Hackenberg et al.’s algorithm using stringent criteria are shorter and have stronger features and lower methylation level. In addition, we used the genome-wide base-resolution methylation profile in two cell lines to show that genes with a lower methylation level at the promoter-associated CpG islands tend to express in more tissues and have stronger expression. Our results validated that the DNA methylation of promoter-associated CpG islands suppresses gene expression at the genome level.

scholarly journals Mining of Brassica-Specific Genes (BSGs) and Their Induction in Different Developmental Stages and under Plasmodiophora brassicae Stress in Brassica rapa

2018 ◽  
Vol 19 (7) ◽  
pp. 2064 ◽  
Author(s):  
Mingliang Jiang ◽  
Xiangshu Dong ◽  
Hong Lang ◽  
Wenxing Pang ◽  
Zongxiang Zhan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brassica Rapa ◽  
Developmental Stages ◽  
Plasmodiophora Brassicae ◽  
Expression Patterns ◽  
Gc Content ◽  
Biological Information ◽  
Lower Percentage ◽  
Orphan Genes ◽  
Conserved Genes

Orphan genes, also called lineage-specific genes (LSGs), are important for responses to biotic and abiotic stresses, and are associated with lineage-specific structures and biological functions. To date, there have been no studies investigating gene number, gene features, or gene expression patterns of orphan genes in Brassica rapa. In this study, 1540 Brassica-specific genes (BSGs) and 1824 Cruciferae-specific genes (CSGs) were identified based on the genome of Brassica rapa. The genic features analysis indicated that BSGs and CSGs possessed a lower percentage of multi-exon genes, higher GC content, and shorter gene length than evolutionary-conserved genes (ECGs). In addition, five types of BSGs were obtained and 145 out of 529 real A subgenome-specific BSGs were verified by PCR in 51 species. In silico and semi-qPCR, gene expression analysis of BSGs suggested that BSGs are expressed in various tissue and can be induced by Plasmodiophora brassicae. Moreover, an A/C subgenome-specific BSG, BSGs1, was specifically expressed during the heading stage, indicating that the gene might be associated with leafy head formation. Our results provide valuable biological information for studying the molecular function of BSGs for Brassica-specific phenotypes and biotic stress in B. rapa.

scholarly journals DISRUPTION OF CPG ISLAND-MEDIATED CHROMATIN ARCHITECTURE AND TRANSCRIPTIONAL HOMEOSTASIS DURING AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S208-S208
Author(s):  
Samuel Beck ◽  
Junyeong Lee
Keyword(s):  
Large Scale ◽  
Cpg Island ◽  
Expression Patterns ◽  
Cpg Islands ◽  
Nuclear Lamina ◽  
The Body ◽  
Chromatin Architecture ◽  
Age Related ◽  
Dna Elements ◽  
Computational Analyses

Abstract Aging causes the global disorganization of nuclear chromatin architecture. In a normal young nucleus, silent heterochromatin is associated with the nuclear lamina layer underlying nuclear envelope, thus spatially separated from euchromatin at the nuclear center. Notably, aging causes the disruption of nuclear lamina and the decondensation of associated heterochromatin. However, it is not clearly understood how these changes of chromatin architectures contribute to age-related diseases. Through large-scale computational analyses, we present that CpG islands (CGIs) give important clues to answering this question. CGIs are DNA elements with high Cytosine-phosphate-Guanine dinucleotide frequencies. In human, about 60% of total genes contain CGIs at their promoters (CGI+ genes) and are broadly expressed throughout the body. The other 40% of genes that do not have CGIs (CGI- genes) exhibit tissue-restricted expression patterns. Our results demonstrate that, in normal young nuclei, only CGI- genes can reside within lamina-associated heterochromatin when transcriptionally inactive, while CGI+ genes associate with nuclear central euchromatin even when they are repressed. In parallel, we show that age-associated heterochromatin decondensation can specifically de-repress tissue-specific CGI- genes leading to their uncontrolled expressions. Our results further demonstrate that global misregulation of CGI- genes increases the noise in gene transcription that, in turn, causes the loss of cellular identities during aging. Taken together, our study establishes critical implication of CGI-mediated chromatin architecture in age-associated degenerative changes and loss of tissue homeostasis.

scholarly journals Limit cycle dynamics can guide the evolution of gene regulatory networks towards point attractors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stuart P. Wilson ◽  
Sebastian S. James ◽  
Daniel J. Whiteley ◽  
Leah A. Krubitzer
Keyword(s):  
Gene Expression ◽  
Limit Cycles ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Specific Gene ◽  
Boolean Models ◽  
A Genome ◽  
Order Of Magnitude ◽  
Accelerate Evolution

AbstractDevelopmental dynamics in Boolean models of gene networks self-organize, either into point attractors (stable repeating patterns of gene expression) or limit cycles (stable repeating sequences of patterns), depending on the network interactions specified by a genome of evolvable bits. Genome specifications for dynamics that can map specific gene expression patterns in early development onto specific point attractor patterns in later development are essentially impossible to discover by chance mutation alone, even for small networks. We show that selection for approximate mappings, dynamically maintained in the states comprising limit cycles, can accelerate evolution by at least an order of magnitude. These results suggest that self-organizing dynamics that occur within lifetimes can, in principle, guide natural selection across lifetimes.

72 HISTONE METHYLATION AND GENE EXPRESSION PATTERNS IN PRE-IMPLANTATION EMBRYOS DERIVED FROM INTRA- AND INTER-SPECIES NUCLEAR TRANSFER

2006 ◽  
Vol 18 (2) ◽  
pp. 144
Author(s):  
W. Shi ◽  
F. Yang ◽  
E. Wolf ◽  
V. Zakharchenko
Keyword(s):  
Gene Expression ◽  
Histone Methylation ◽  
Methylation Level ◽  
Dynamic Change ◽  
Expression Patterns ◽  
Mouse Embryos ◽  
Bovine Embryos ◽  
Cell Stage ◽  
Rabbit Embryos

The differential epigenetic changes in embryos from different species provide a model to study how the nucleus from one species interacts with cytoplasm from another species. In this study we examined histone methylation at lysine 9 of histone 3 (K9H3) and lysine 20 of histone H4 (K20H4) and the expression levels of three early development-related genes (Oct-4, Hsp 70.1 and Hprt) in individual intra- and inter-species cloned and control embryos at the 1-, 2-, 4- and 8-cell stages. Mouse fetal fibroblast (MFF) nuclei were transferred into mouse, bovine, or rabbit oocytes. As control, we used in vivo derived (mouse and rabbit) or in vitro-produced (bovine) embryos. Histone methylation was detected by anti-MeK9H3 and anti-MeK20H4 antibodies. Gene expression analysis was performed using a quantitative RT-PCR technique (Daniels et al. 2000 Biol. Reprod. 63, 1034-1040). Data were analyzed by Student's t-test. No embryos from inter-species cloning (MFF-bovine and MFF-rabbit) survived beyond the 8-12 cell stage. MFF-mouse and MFF-bovine embryos exhibited demethylation of K9H3 and K20H4 at the 2-cell stage and the methylation level was increased at the 4-cell stage, but no demethylation was observed at the 2-cell stage of MFF-rabbit embryos and the methylation level in these embryos was significantly higher than that of in vivo rabbit embryos. The level of Oct-4 mRNA was low at the 1- and 2-cell stages of in vivo mouse embryos and increased at the 8-cell stage. No significant increase in Oct-4 transcript was detected at the 8-cell stage of inter-species cloned embryos. The expression of Hsp 70.1 in in vivo mouse embryos was increased at the 2-cell stage and decreased to a level similar to that in the zygote at the 8-cell stage. In cloned embryos, Hsp 70.1 transcripts were also increased at the 2-cell stage, but there was no significant decrease of Hsp70.1 mRNA abundance at the 8-cell stage of inter-species embryos as compared to the corresponding 2-cell stage. For MFF-mouse embryos, Hsp 70.1 expression was increased at the 2-cell stage, but at the 8-cell stage the transcript level was at the level similar to that in inter-species clones. Hprt expression was increased at the 8-cell stage of in vivo mouse embryos. The dynamic change of Hprt transcript in MFF-mouse embryos was not significantly different from that of in vivo mouse embryos, but no significant change of Hprt expression occurred in the development of MFF-bovine and MFF-rabbit embryos. Differential epigenetic characteristics of mouse somatic nucleus after transfer into oocytes from different species suggest the existence of incompatibilities of nuclear-cytoplasm interaction between distantly related species. This abnormal interaction at the time of genome activation may affect normal development. This work was supported by the Bayerische Forschungsstiftung and by Therapeutic Human Polyclonals, Inc.

scholarly journals Integrated Analysis of mRNA Expression, CpG Island Methylation, and Polymorphisms in the MITF Gene in Ducks (Anas platyrhynchos)

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Ruiyi Lin ◽  
Weimin Lin ◽  
Shiye Zhou ◽  
Qiaohui Chen ◽  
Jiahua Pan ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Methylation Level ◽  
Cpg Island ◽  
Methylation Status ◽  
Cpg Islands ◽  
Plumage Coloration ◽  
Integrated Analysis ◽  
Nucleotide Polymorphisms ◽  
White Feather ◽  
Black Feather

Microphthalmia-associated transcription factor (MITF) is a key regulator for the development and function of melanocytes in skin, eye, and plumage pigmentations. Thus, the MITF was selected as a candidate gene associated with plumage coloration in ducks. This study analyzed the mRNA expression, promoter methylation, and polymorphisms in the MITF gene in ducks with different plumage colors (Putian Black, Putian White, Liancheng White, and Longsheng Jade-green). No expression of the MITF melanin-specific isoform (MITF-M) was detected in white feather bulbs. By contrast, the mRNA expression levels of MITF-M were high in black feather bulbs. Bioinformatics analysis showed that two CpG islands were present in the promoter region of the MITF gene. The methylation level of the second CpG island was significantly lower in black feather bulbs than in white feather bulbs. However, the methylation level of the first CpG island was not different among the feather bulbs with various colors except Liancheng White feather bulbs. The methylation status of the whole CpG island significantly and negatively correlated with the mRNA expression of MITF-M (P<0.05). Furthermore, four novel SNPs (single nucleotide polymorphisms) were identified in the 5′UTR, exon 4, intron 7, and intron 8 of the MITF gene. Allele T in g.39807T>G and allele G in g.40862G>A were the predominant alleles only found in Putian White, whereas the variant A allele in g.32813G>A exhibited a high allele frequency in Liancheng White. Collectively, these results contributed to the understanding of the function of the MITF gene in duck plumage coloration.

Genome-Wide DNA Methylation Analysis Shows Enrichment of Differential Methylation in “Open Seas” and Enhancers and Reveals Hypomethylation in DNMT3A Mutated Cytogenetically Normal AML (CN-AML)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 653-653 ◽  
Author(s):  
Ying Qu ◽  
Andreas Lennartsson ◽  
Verena I. Gaidzik ◽  
Stefan Deneberg ◽  
Sofia Bengtzén ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cpg Island ◽  
Cpg Islands ◽  
Differential Methylation ◽  
Methylation Analysis ◽  
Cpg Sites ◽  
Genome Wide ◽  
Genomic Regions ◽  
Methylation Patterns

Abstract Abstract 653 DNA methylation is involved in multiple biologic processes including normal cell differentiation and tumorigenesis. In AML, methylation patterns have been shown to differ significantly from normal hematopoietic cells. Most studies of DNA methylation in AML have previously focused on CpG islands within the promoter of genes, representing only a very small proportion of the DNA methylome. In this study, we performed genome-wide methylation analysis of 62 AML patients with CN-AML and CD34 positive cells from healthy controls by Illumina HumanMethylation450K Array covering 450.000 CpG sites in CpG islands as well as genomic regions far from CpG islands. Differentially methylated CpG sites (DMS) between CN-AML and normal hematopoietic cells were calculated and the most significant enrichment of DMS was found in regions more than 4kb from CpG Islands, in the so called open sea where hypomethylation was the dominant form of aberrant methylation. In contrast, CpG islands were not enriched for DMS and DMS in CpG islands were dominated by hypermethylation. DMS successively further away from CpG islands in CpG island shores (up to 2kb from CpG Island) and shelves (from 2kb to 4kb from Island) showed increasing degree of hypomethylation in AML cells. Among regions defined by their relation to gene structures, CpG dinucleotide located in theoretic enhancers were found to be the most enriched for DMS (Chi χ2<0.0001) with the majority of DMS showing decreased methylation compared to CD34 normal controls. To address the relation to gene expression, GEP (gene expression profiling) by microarray was carried out on 32 of the CN-AML patients. Totally, 339723 CpG sites covering 18879 genes were addressed on both platforms. CpG methylation in CpG islands showed the most pronounced anti-correlation (spearman ρ =-0.4145) with gene expression level, followed by CpG island shores (mean spearman rho for both sides' shore ρ=-0.2350). As transcription factors (TFs) have shown to be crucial for AML development, we especially studied differential methylation of an unbiased selection of 1638 TFs. The most enriched differential methylation between CN-AML and normal CD34 positive cells were found in TFs known to be involved in hematopoiesis and with Wilms tumor protein-1 (WT1), activator protein 1 (AP-1) and runt-related transcription factor 1 (RUNX1) being the most differentially methylated TFs. The differential methylation in WT 1 and RUNX1 was located in intragenic regions which were confirmed by pyro-sequencing. AML cases were characterized with respect to mutations in FLT3, NPM1, IDH1, IDH2 and DNMT3A. Correlation analysis between genome wide methylation patterns and mutational status showed statistically significant hypomethylation of CpG Island (p<0.0001) and to a lesser extent CpG island shores (p<0.001) and the presence of DNMT3A mutations. This links DNMT3A mutations for the first time to a hypomethylated phenotype. Further analyses correlating methylation patterns to other clinical data such as clinical outcome are ongoing. In conclusion, our study revealed that non-CpG island regions and in particular enhancers are the most aberrantly methylated genomic regions in AML and that WT 1 and RUNX1 are the most differentially methylated TFs. Furthermore, our data suggests a hypomethylated phenotype in DNMT3A mutated AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Potential Role of Genetic Assimilation during Maize Domestication

2017 ◽  
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.

scholarly journals Genome-Wide Phylogenetic Analysis, Expression Pattern, and Transcriptional Regulatory Network of the Pig C/EBP Gene Family

2021 ◽  
Vol 17 ◽  
pp. 117693432110413
Author(s):  
Chaoxin Zhang ◽  
Tao Wang ◽  
Tongyan Cui ◽  
Shengwei Liu ◽  
Bing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phylogenetic Analysis ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Genome Wide ◽  
A Genome

The CCAAT/enhancer binding protein (C/EBP) transcription factors (TFs) regulate many important biological processes, such as energy metabolism, inflammation, cell proliferation etc. A genome-wide gene identification revealed the presence of a total of 99 C/EBP genes in pig and 19 eukaryote genomes. Phylogenetic analysis showed that all C/EBP TFs were classified into 6 subgroups named C/EBPα, C/EBPβ, C/EBPδ, C/EBPε, C/EBPγ, and C/EBPζ. Gene expression analysis showed that the C/EBPα, C/EBPβ, C/EBPδ, C/EBPγ, and C/EBPζ genes were expressed ubiquitously with inconsistent expression patterns in various pig tissues. Moreover, a pig C/EBP regulatory network was constructed, including C/EBP genes, TFs and miRNAs. A total of 27 feed-forward loop (FFL) motifs were detected in the pig C/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to FFL sub-network were analyzed in 27 adult pig tissues. Certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that C/EBP and its target genes are involved in many important biological pathways. These results provide valuable information that clarifies the evolutionary relationships of the C/EBP family and contributes to the understanding of the biological function of C/EBP genes.

Methylation of Progesterone Receptor Promoter-Associated CpG Island in Polycythemia Vera and Related Myeloproliferative Disorders.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3507-3507
Author(s):  
Jaroslav Jelinek ◽  
Srdan Verstovsek ◽  
Carlos E. Bueso-Ramos ◽  
Josef T. Prchal ◽  
Jean-Pierre J. Issa
Keyword(s):  
Progesterone Receptor ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Cpg Island ◽  
Cpg Islands ◽  
Myeloproliferative Disorders ◽  
Receptor Expression ◽  
Quantitative Detection ◽  
Jak2 Mutation ◽  
A Genome

Abstract Polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (MF) are clonal myeloproliferative disorders (MPD). A recently discovered activating mutation of JAK2 tyrosine kinase has been found in most patients with polycythemia vera (PV), in about half of those with essential thrombocythemia (ET) and myelofibrosis (MF), and in 10–20% patients with chronic myelomonocytic leukemia, Philadelphia-negative CML, atypical or unclassified MPD and megakaryocytic leukemia. It is not known what other factors determine the disease phenotype of PV, MF, and other MPD, and what factors other than JAK2 lead to disease progression. Very little is known about epigenetic changes in PV. DNA methylation of promoter-associated CpG islands is a well-recognized mechanism of epigenetic silencing used by tumors for evasion from regulatory mechanisms, and it is an alternative to genetic lesions in cancer causation. Using a genome-wide screen for differentially methylated CpG islands, we found methylation of progesterone receptor promoter region (PGR) in PV granulocytes. We then developed pyrosequencing assays for quantitative detection of PGR methylation in bisulfite-treated PCR-amplified DNA. The PGR methylation above normal control levels was observed in ET (2/12 patients, 17%), PV (10/22 patients, 45%), MF (8/12 patients, 67%), and patients with acute myeloid leukemia and antecedent PV (6/7 patients, 86%). We compared the levels of PGR methylation in MPD with the mutation status of JAK2. The 1849G&gt;T JAK2 mutation was present in 16/27 (59%) MPD patients with unmethylated PGR and 21/26 (80%) patients with methylated PGR; the difference not statistically significant; p=0.135. The role of progesterone receptor signaling in hematopoiesis is not known. Using real time quantitative RT-PCR assay for progesterone receptor expression we found detectable levels in granulocytes from 4/5 normal individuals while the expression in granulocytes from 5/5 PV patients was not detectable. To assess the functional significance of progesterone receptor silencing, we explored the effect of mifepristone, a progesterone receptor antagonist, on the response of BFU-E progenitors to erythropoietin. Mifepristone increased the sensitivity of BFU-E progenitors from normal blood to low concentrations of erythropoietin (60–250 mU/ml) suggesting that disabling of progesterone receptor may increase the response of hematopoietic cells to proliferative stimuli. In conclusion, our data show that PGR methylation is present in half of PV patients and it is even more frequent in MF and PV transformed to AML. Silencing of progesterone receptor by methylation may be an epigenetic change contributing to MPD phenotype and transformation to leukemia.

scholarly journals Assessing Gene Expression and Methylation of KMT2D and IGF2 Genes in Patients with Non-Small Cell Lung Cancer

2018 ◽  
Vol 7 (1) ◽  
pp. 55
Author(s):  
Arash Matin Ahmadi ◽  
Hessamodin Ghasemi ◽  
Sajad Nooshin ◽  
Zoofa Zayani ◽  
Shohreh Zare Karizi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Methylation Level ◽  
Cpg Islands ◽  
Regulation Of Gene Expression ◽  
Tumor Development ◽  
Gene Promoter ◽  
Cancer Tissue ◽  
Lung Carcinogenesis ◽  
Igf2 Gene

Background: Aberrant promoter methylation of CpG islands is an important mechanism for regulation of gene expression. Recent data suggest that epigenetic abnormalities may occur very early in lung carcinogenesis. Systemic methylation changes may be a diagnostic marker for tumor development or prognosis. In this study, the expression and methylation of KMT2D and IGF2 genes were investigated in the lung cancer tissue compared to the adjacent normal tissue.Methods: The status of methylation of KMT2D and IGF2 genes were investigated in 30 patients with NSCLC after genomic DNA extraction using bisulfite treatment and MS-HRM method and the expression of these genes were checked by Real-Time PCR method in same samples.Results: For KMT2D gene, the expression and methylation level increased in 46.6% and 6.67% (respectively) for tumor samples comparison with normal samples (P>0.05). Also, for IGF2 gene 50% tumor samples overexpressed and 50% tumor samples showed that reduced expression comparison with the normal samples (P>0.05). In addition, 96.66% of tumor tissues did not show any change in methylation level for IGF2 gene promoter (P>0.05).Conclusion: This study showed that expression and methylation level of KMT2D and IGF2 genes did not change in NSCLC tumor samples compared to normal samples. However, this study was designed as a pilot study, and further investigations are required to confirm our findings.

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