Difference in potential DNA methylation impact on gene expression between fast- and slow-type myofibers

2021 ◽  
Author(s):  
Mika Oe ◽  
Koichi Ojima ◽  
Susumu Muroya
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Cpg Methylation ◽  
Alternative Promoter ◽  
Epigenetic Mechanism ◽  
Gene Body ◽  
Regulated Expression ◽  
Slow Type ◽  
Promoter Usage ◽  
Myofiber Type

Skeletal muscles are comprised of two major types of myofibers, fast and slow. It is hypothesized that once myofiber type is determined, muscle fiber-type specificity is maintained by an epigenetic mechanism, however, this remains poorly understood. To address this, we conducted a comprehensive CpG methylation analysis with a reduced representation of bisulfite sequencing (RRBS). Using GFP-myh7 mouse, we visually distinguished and separately pooled slow-type and myh7-negative fast-type fibers for analyses. A total of 31,967 and 26,274 CpGs were hypermethylated by ≥10% difference in the fast- and slow-type fibers, respectively. Notably, the number of promoter-hypermethylated genes with down-regulated expression in the slow-type fibers was 3.5 times higher than that in the fast-type fibers. Gene bodies of the fast-type-specific myofibrillar genes Actn3, Tnnt3, Tnni2, Tnnc2, and Tpm1 were hypermethylated in the slow-type fibers, whereas those of the slow-type-specific genes Myh7, Tnnt1, and Tpm3 were hypermethylated in the fast-type fibers. Each of the instances of gene hypermethylation was associated with the respective down-regulated expression. In particular, a relationship between CpG methylation sites and the transcription variant distribution of Tpm1 was observed, suggesting a regulation of Tpm1 alternative promoter usage by gene body CpG methylation. An association of hypermethylation with the regulation of gene expression was also observed in Wdr70, and transcription factors Sim2 and Tbx1. These results suggest not only a myofiber type-specific regulation of gene expression and alternative promoter usage by gene body CpG methylation, but also a dominant effect of promoter-hypermethylation on the gene expressions in slow myofibers.

scholarly journals The Emerging Role of ATP-Dependent Chromatin Remodeling in Memory and Substance Use Disorders

2020 ◽  
Vol 21 (18) ◽  
pp. 6816
Author(s):  
Alberto J. López ◽  
Julia K. Hecking ◽  
André O. White
Keyword(s):  
Gene Expression ◽  
Substance Use ◽  
Substance Use Disorders ◽  
Chromatin Remodeling ◽  
Cell Function ◽  
Regulation Of Gene Expression ◽  
Memory Formation ◽  
Epigenetic Mechanism ◽  
Chromatin Remodelers ◽  
Histone Modifying Enzymes

Long-term memory formation requires coordinated regulation of gene expression and persistent changes in cell function. For decades, research has implicated histone modifications in regulating chromatin compaction necessary for experience-dependent changes to gene expression and cell function during memory formation. Recent evidence suggests that another epigenetic mechanism, ATP-dependent chromatin remodeling, works in concert with the histone-modifying enzymes to produce large-scale changes to chromatin structure. This review examines how histone-modifying enzymes and chromatin remodelers restructure chromatin to facilitate memory formation. We highlight the emerging evidence implicating ATP-dependent chromatin remodeling as an essential mechanism that mediates activity-dependent gene expression, plasticity, and cell function in developing and adult brains. Finally, we discuss how studies that target chromatin remodelers have expanded our understanding of the role that these complexes play in substance use disorders.

scholarly journals CG gene body DNA methylation changes and evolution of duplicated genes in cassava

2015 ◽  
Vol 112 (44) ◽  
pp. 13729-13734 ◽  
Author(s):  
Haifeng Wang ◽  
Getu Beyene ◽  
Jixian Zhai ◽  
Suhua Feng ◽  
Noah Fahlgren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Gene Copy ◽  
Gene Body ◽  
Duplicated Genes ◽  
Gene Body Methylation ◽  
Substantial Impact ◽  
Tropical Regions

DNA methylation is important for the regulation of gene expression and the silencing of transposons in plants. Here we present genome-wide methylation patterns at single-base pair resolution for cassava (Manihot esculenta, cultivar TME 7), a crop with a substantial impact in the agriculture of subtropical and tropical regions. On average, DNA methylation levels were higher in all three DNA sequence contexts (CG, CHG, and CHH, where H equals A, T, or C) than those of the most well-studied model plant Arabidopsis thaliana. As in other plants, DNA methylation was found both on transposons and in the transcribed regions (bodies) of many genes. Consistent with these patterns, at least one cassava gene copy of all of the known components of Arabidopsis DNA methylation pathways was identified. Methylation of LTR transposons (GYPSY and COPIA) was found to be unusually high compared with other types of transposons, suggesting that the control of the activity of these two types of transposons may be especially important. Analysis of duplicated gene pairs resulting from whole-genome duplication showed that gene body DNA methylation and gene expression levels have coevolved over short evolutionary time scales, reinforcing the positive relationship between gene body methylation and high levels of gene expression. Duplicated genes with the most divergent gene body methylation and expression patterns were found to have distinct biological functions and may have been under natural or human selection for cassava traits.

scholarly journals The impact of Piscirickettsia Salmonis infection on genome-wide DNA methylation profile in Atlantic Salmon

2021 ◽  
Author(s):  
Robert Mukiibi ◽  
Carolina Peñaloza ◽  
Alejandro Gutierrez ◽  
José M. Yáñez ◽  
Ross D. Houston ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Atlantic Salmon ◽  
Negative Correlation ◽  
Regulation Of Gene Expression ◽  
Head Kidney ◽  
Epigenetic Mechanism ◽  
Piscirickettsia Salmonis ◽  
The Impact

Salmon rickettsial septicaemia (SRS), caused by the intracellular bacteria Piscirickettsia Salmonis, generates significant mortalities to farmed Atlantic salmon, particularly in Chile. Due to its economic importance, a wealth of research has focussed on the biological mechanisms underlying pathogenicity of P. salmonis, the host response, and genetic variation in host resistance. DNA methylation is a fundamental epigenetic mechanism that influences almost every biological process via the regulation of gene expression and plays a key role in the response of an organism to stimuli. In the current study, the role of head kidney and liver DNA methylation in the response to P. salmonis infection was investigated in a commercial Atlantic salmon population. A total of 66 salmon were profiled using reduced representation bisulphite sequencing (RRBS), with head kidney and liver methylomes compared between infected animals (3 and 9 days post infection) and uninfected controls. These included groups of salmon with divergent (high or low) breeding values for resistance to P. salmonis infection, to examine the influence of genetic resistance. Head kidney and liver showed organ-specific global methylation patterns, but with similar distribution of methylation across gene features. Integration of methylation with RNA-Seq data revealed that methylation levels predominantly showed a negative correlation with gene expression, although positive correlations were also observed. Methylation within the first exon showed the strongest negative correlation with gene expression. A total of 911 and 813 differentially methylated CpG sites were identified between infected and control samples in the head kidney at 3 and 9 days respectively, whereas only 30 and 44 sites were differentially methylated in the liver. Differential methylation in the head kidney was associated with immunological processes such as actin cytoskeleton regulation, phagocytosis, endocytosis and pathogen associated pattern receptor signaling. We also identified 113 and 48 differentially methylated sites between resistant and susceptible fish in the head kidney and liver respectively. Our results contribute to the growing understanding of the role of methylation in regulation of gene expression and response to infectious diseases, and in particular reveal key immunological functions regulated by methylation in Atlantic salmon in response to P. salmonis.

scholarly journals Cap analysis of gene expression (CAGE) sequencing reveals alternative promoter usage in complex disease

2021 ◽  
Author(s):  
Sonal Dahale ◽  
Jorge Ruiz-Orera ◽  
Jan Silhavy ◽  
Norbert Hubner ◽  
Sebastiaan van Heesch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Disease ◽  
Complex Diseases ◽  
Alternative Promoter ◽  
Brown Norway ◽  
Specific Gene ◽  
Insulin Receptor Gene ◽  
Promoter Usage ◽  
Cap Analysis

The role of alternative promoter usage in tissue specific gene expression has been well established, however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) tag sequencing from the left ventricle (LV) of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, the Brown Norway (BN) to understand role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites (TSS) in the rat LV, including 1,970 novel cardiac TSS resulting in new transcripts. We identified 27 genes with alternative promoter usage between SHR and BN which could lead to protein isoforms differing at the amino terminus between two strains. Additionally, we identified 475 promoter switching events where a shift in TSS usage was within 100bp between SHR and BN, altering length of the 5 prime UTR. Genomic variants located in the shifting promoter regions showed significant allelic imbalance in F1 crosses, confirming promoter shift. We found that the insulin receptor gene (Insr) showed a switch in promoter usage between SHR and BN in heart and liver. The Insr promoter shift was significantly associated with insulin levels and blood pressure within a panel of BXH/HXB recombinant inbred (RI) rat strains. This suggests that the hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.

scholarly journals Peptide Regulation of Gene Expression: A Systematic Review

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7053
Author(s):  
Vladimir Khatskelevich Khavinson ◽  
Irina Grigor’evna Popovich ◽  
Natalia Sergeevna Linkova ◽  
Ekaterina Sergeevna Mironova ◽  
Anastasiia Romanovna Ilina
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Epigenetic Mechanism ◽  
Short Peptides ◽  
Gene Promoters ◽  
Amino Acid Residues ◽  
Sequence Recognition ◽  
Wide Range ◽  
The Status ◽  
Synthetic Reactions

Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such action of peptides involves their ability to regulate gene expression and protein synthesis in plants, microorganisms, insects, birds, rodents, primates, and humans. Short peptides, consisting of 2–7 amino acid residues, can penetrate into the nuclei and nucleoli of cells and interact with the nucleosome, the histone proteins, and both single- and double-stranded DNA. DNA–peptide interactions, including sequence recognition in gene promoters, are important for template-directed synthetic reactions, replication, transcription, and reparation. Peptides can regulate the status of DNA methylation, which is an epigenetic mechanism for the activation or repression of genes in both the normal condition, as well as in cases of pathology and senescence. In this context, one can assume that short peptides were evolutionarily among the first signaling molecules that regulated the reactions of template-directed syntheses. This situation enhances the prospects of developing effective and safe immunoregulatory, neuroprotective, antimicrobial, antiviral, and other drugs based on short peptides.

Analysis of DNA Methylation and Transcription During Granulopoiesis Reveals Timed Methylation Changes in Low CpG Areas That Correlate with Changed Transcriptional Activity.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2334-2334
Author(s):  
Rönnerblad Michelle ◽  
Olofsson Tor ◽  
Iyadh Douagi ◽  
Sören Lehmann ◽  
Karl Ekwall ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Conflicts Of Interest ◽  
Cell Types ◽  
Cpg Methylation ◽  
Epigenetic Mechanism ◽  
450K Array ◽  
Chi Square ◽  
Heterochromatin Formation ◽  
Chi Square Test

Abstract Abstract 2334 Accumulating evidence demonstrates that epigenetic changes, including DNA methylation play a central role in differentiation, providing cellular memory and stabilizing lineage choice in hematopoiesis1–3. DNA methylation is an important epigenetic mechanism involved in transcriptional regulation, heterochromatin formation and the normal development of many organisms. In this study we investigated the DNA methylome and transcriptome of human cells in four separate differentiation stages in granulopoiesis, ranging from the multipotent Common Myeloid progenitor (CMP) to terminally differentiated bone marrow neutrophils (PMN). To this end we employed HumanMethylation 450 BeadChip (450K array) from Illumina with extensive genomic coverage and mRNA expression arrays (Illumina). Temporally distinct methylation changes during granulopoiesis Differential methylation between two cell stages was defined as an average difference in β value of at least 0.17 (p ≤ 0.05). We detected 12132 DMSs during granulopoiesis. Of these the majority showed decreased methylation during granulopoeisis (10771 CpGs) and a smaller set gained methylation (1658 CpGs). Strikingly, increases in methylation predominantly occur between CMP and GMP, the two least mature cell types. Some CpGs also show increased methylation in the GMP-PMC transition, while very few CpG sites increase at the final stage of differentiation from PMC to PMN. Although reduction of methylation occurs at all stages of granulopoiesis, the greatest change is between GMP and PMC. It is striking that the DNA methylation patterns preferentially change at points of lineage restriction, and that the greatest change occurs upon loss of oligopotency between GMP and PMC. DMSs within CGIs were greatly underrepresented (p<0.001 with chi-square test), while DMSs were overrepresented in shelves (p<0.001) and open sea (p<0.001). Thus, methylation appears to be more dynamic outside of CGIs during granulocytic development. For all regions the variation within enhancers was greater than outside of enhancers indicating greater methylation changes in enhancers compared to non-enhancers. In addition, CpGs in enhancer regions are significantly enriched in the list of DMSs (p<0.001, chi-square test) further supporting the observation that enhancer regions display dynamic DNA methylation changes during granulopoiesis. Changes in gene expression correlate with DNA methylation changes There was a significant overlap between genes showing decreased methylation and genes with increased expression as well as for the reverse comparison between genes with increased methylation and decreased expression. Thus, support a general anticorrelation between DNA methylation and gene expression. Azurophilic granule proteins showed increased expression peaking in PMC and a rapid decrease toward PMN. CpG methylation levels for those genes decreased concomitantly with the peak in expression. We report cell population specific changes of DNA methylation levels. The main reduction of CpG methylation coincides with the loss of oligopotency at the transition from GMP-PMC. This suggests a role of DNA methylation in regulating cell plasticity and lineage choice. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Changes in the methylation level of microRNA genes as a factor of breast cancer development and progression

2021 ◽  
pp. 4-11
Author(s):  
Е.А. Филиппова ◽  
А.М. Бурденный ◽  
С.С. Лукина ◽  
Н.А. Иванова ◽  
И.В. Пронина ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Methylation Level ◽  
Molecular Subtype ◽  
Regulation Of Gene Expression ◽  
Epigenetic Mechanism ◽  
Cancer Tissue ◽  
Aberrant Methylation ◽  
Suppressor Genes ◽  
Mirna Genes

Введение. Метилирование как процесс эпигенетической регуляции экспрессии генов является важнейшим в поддержании геномной стабильности. В норме этот процесс определяет подавление активности онкогенов и поддержание работы супрессоров опухолевого роста. Другим важнейшим эпигенетическим регулятором являются микроРНК. Нарушения метилирования CpG-островков в промоторных районах генов, кодирующих микроРНК, являются важнейшим фактором онкогенеза. Цель - расширение спектра генов микроРНК гиперметилируемых при раке молочной железы и изучение их связи с метастазированием и иммуногистохимическим статусом опухоли. Методика. В настоящей работе был проведен отбор ряда генов микроРНК, изменяющих уровень метилирования при раке молочной железы. Методом количественной метилспецифичной ПЦР на представительной выборке из 70 парных образцов рака молочной железы изучен уровень метилирования 8 генов микроРНК, ассоциированных с раком молочной железы: MIR107, MIR124-2, MIR1258, MIR130B, MIR137, MIR191, MIR203А, MIR339. Результаты. Показано статистически значимое увеличение уровня метилирования в опухолевой ткани РМЖ по сравнению с гистологически нормальной тканью молочной железы для генов MIR107, MIR124-2, MIR1258, MIR130В, MIR137, MIR339 и снижение уровня метилирования для гена MIR191. Кроме того, показано статистически значимое увеличение уровня метилирования на III-IV (поздних) стадиях РМЖ для генов MIR107, MIR1258, MIR130В, MIR137, MIR339, в опухолях с большим размером - MIR107, MIR1258, MIR130В, MIR137, MIR339, с низким уровнем дифференцировки - MIR124-2, с наличием метастазов в лимфатические узлы - MIR107, MIR1258, MIR137, MIR339. Опухоли, не экспрессирующие рецептор прогестерона (PR), имеют статистически значимо более высокий уровень метилирования генов MIR137, MIR339. Заключение. Таким образом, определены новые молекулярные показатели прогрессии РМЖ и биомаркеры, которые могут быть использованы при дифференциальной диагностике молекулярного подтипа РМЖ. Background. Methylation, as an epigenetic mechanism for regulation of gene expression, is crucial for the genome stability. Normally, this process is characterized by the ability to silence the oncogene activity and to support the action of suppressor genes. MicroRNAs (miRNAs) are another key epigenetic regulator of gene expression. Aberrant methylation of CpG islands in promoter regions of the genes that code miRNAs is the most important oncogenic factor. Aim. To expand the spectrum of miRNA genes hypermethylated in breast cancer and to study their relationship with metastasis and immunohistochemical status of the tumor. Methods. MiRNA tumor suppressor genes were selected that changed their methylation level in breast cancer patients. Using the method of quantitative methylation-specific PCR, the methylation level of eight miRNA genes associated with breast cancer was studied on a representative set of 70 paired breast cancer samples: MIR107, MIR124-2, MIR1258, MIR130B, MIR137, MIR191, MIR203A, and MIR339. Results. The methylation level of the genes MIR-107, MIR124-2, MIR1258, MIR130B, MIR137, MIR339 was significantly higher in breast cancer tissue compared to normal breast tissue whereas for the gene MIR191, it was significantly lower. Also, the methylation levels of genes MIR107, MIR1258, MIR130B, MIR137, and MIR339 were significantly increased at stages III-IV (advanced) breast cancer; in large tumors, the methylation levels were increased for MIR107, MIR1258, MIR130B, MIR137, and MIR339; in poorly differentiated tumors, the methylation level was increased for MIR124-2; and in the presence of lymph node metastases, for MIR107, MIR1258, MIR-137, and MIR-339. Tumors not expressing the progesterone receptor (PR) had a higher methylation level of MIR137 and MIR339. Conclusion. The study determined new molecular indicators for breast cancer progression and identified biomarkers that may be used in the differential diagnosis of breast cancer molecular subtype.

Protein inheritance and regulation of gene expression in yeast

2010 ◽  
Vol 8 (4) ◽  
pp. 10-16
Author(s):  
Ludmila N Mironova
Keyword(s):  
Gene Expression ◽  
Rapid Development ◽  
Good Reason ◽  
Regulation Of Gene Expression ◽  
Epigenetic Mechanism ◽  
Genetic Determinants ◽  
Phenotypic Manifestation ◽  
Cellular Population ◽  
Protein Nature

Prions of lower eukaryotes are genetic determinants of protein nature. Last years are marked by rapid development of the conception of prion inheritance. The list of yeast proteins, which have been shown to exist in the prion form in vivo, and phenotypic manifestation of prions provide good reason to believe that protein prionization may represent epigenetic mechanism regulating adaptability of a single cell and cellular population to environmental conditions.

Genome-wide Differential-based Analysis of the Relationship between DNA Methylation and Gene Expression in Cancer

2019 ◽  
Vol 14 (8) ◽  
pp. 783-792 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Chuanhua Kou ◽  
Shudong Wang ◽  
Yulin Zhang
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epigenetic Modification ◽  
Epigenetic Mechanism ◽  
Gene Body ◽  
Differential Analysis ◽  
Promoter Regions ◽  
Genome Wide ◽  
Significant Difference ◽  
The Relationship

Background:: DNA methylation is an epigenetic modification that plays an important role in regulating gene expression. There is evidence that the hypermethylation of promoter regions always causes gene silencing. However, how the methylation patterns of other regions in the genome, such as gene body and 3’UTR, affect gene expression is unknown. Objective:: The study aimed to fully explore the relationship between DNA methylation and expression throughout the genome-wide analysis which is important in understanding the function of DNA methylation essentially. Method:: In this paper, we develop a heuristic framework to analyze the relationship between the methylated change in different regions and that of the corresponding gene expression based on differential analysis. Results:: To understande the methylated function of different genomic regions, a gene is divided into seven functional regions. By applying the method in five cancer datasets from the Synapse database, it was found that methylated regions with a significant difference between cases and controls were almost uniformly distributed in the seven regions of the genome. Also, the effect of DNA methylation in different regions on gene expression was different. For example, there was a higher percentage of positive relationships in 1stExon, gene body and 3’UTR than in TSS1500 and TSS200. The functional analysis of genes with a significant positive and negative correlation between DNA methylation and gene expression demonstrated the epigenetic mechanism of cancerassociated genes. Conclusion:: Differential based analysis helps us to recognize the change in DNA methylation and how this change affects the change in gene expression. It provides a basis for further integrating gene expression and DNA methylation data to identify disease-associated biomarkers.

Sign in / Sign up

Export Citation Format

Share Document