Control of gene expression by CpG island methylation in normal cells

2004 ◽  
Vol 32 (6) ◽  
pp. 913-915 ◽  
Author(s):  
G. Strathdee ◽  
A. Sim ◽  
R. Brown
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cpg Island ◽  
Expression Patterns ◽  
Critical Role ◽  
Tumour Suppressor Genes ◽  
Normal Cells ◽  
Control Of Gene Expression ◽  
Cpg Island Methylation

The role of DNA methylation in the control of mammalian gene expression has been the subject of intensive research in recent years, partly due to the critical role of CpG island methylation in the inactivation of tumour suppressor genes during the development of cancer. However, this research has also helped elucidate the role that DNA methylation plays in normal cells. At present, it is also clear that DNA methylation forms an important part of the normal cell-regulatory processes that govern gene transcription. Methylation, targeted at CpG islands, is an important part of the mechanisms that govern X-chromosome inactivation; it is also essential for the maintenance of imprinted genes and, at least in some cases, is critical in determining the cell-type-specific expression patterns of genes. Study of these examples will be important in identifying the mechanisms that control targeting of DNA methylation and how these processes are disrupted during disease pathogenesis.

scholarly journals DNA Methylation and Chromatin: Role(s) of Methyl-CpG-Binding Protein ZBTB38

2018 ◽  
Vol 11 ◽  
pp. 251686571881111 ◽  
Author(s):  
Maud de Dieuleveult ◽  
Benoit Miotto
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Mammalian Cells ◽  
Expression Patterns ◽  
Control Of Gene Expression ◽  
Methylated Dna

DNA methylation plays an essential role in the control of gene expression during early stages of development as well as in disease. Although many transcription factors are sensitive to this modification of the DNA, we still do not clearly understand how it contributes to the establishment of proper gene expression patterns. We discuss here the recent findings regarding the biological and molecular function(s) of the transcription factor ZBTB38 that binds methylated DNA sequences in vitro and in cells. We speculate how these findings may help understand the role of DNA methylation and DNA methylation–sensitive transcription factors in mammalian cells.

scholarly journals The Critical Role of miRNAs in Regulation of Flowering Time and Flower Development

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 319
Author(s):  
Saquib Waheed ◽  
Lihui Zeng
Keyword(s):  
Gene Expression ◽  
Flower Development ◽  
Critical Role ◽  
Transcriptional Level ◽  
Control Of Gene Expression ◽  
Non Coding Rnas ◽  
Time Of Year ◽  
Acting In Concert ◽  
Flowering Process

Flowering is an important biological process for plants that ensures reproductive success. The onset of flowering needs to be coordinated with an appropriate time of year, which requires tight control of gene expression acting in concert to form a regulatory network. MicroRNAs (miRNAs) are non-coding RNAs known as master modulators of gene expression at the post-transcriptional level. Many different miRNA families are involved in flowering-related processes such as the induction of floral competence, floral patterning, and the development of floral organs. This review highlights the diverse roles of miRNAs in controlling the flowering process and flower development, in combination with potential biotechnological applications for miRNAs implicated in flower regulation.

scholarly journals Critical Role of Types 2 and 3 Deiodinases in the Negative Regulation of Gene Expression by T3 in the Mouse Cerebral Cortex

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2919-2928 ◽  
Author(s):  
Arturo Hernandez ◽  
Beatriz Morte ◽  
Mónica M. Belinchón ◽  
Ainhoa Ceballos ◽  
Juan Bernal
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Thyroid Hormone ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Control Of Gene Expression ◽  
High Doses ◽  
And Function ◽  
Type 3

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T3 to nuclear receptors. Brain T3 concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T4 and T3. We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T3 led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T3 treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T3 action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T3 concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

scholarly journals Incorporation of DNA methylation into eQTL mapping in African Americans

2020 ◽  
Author(s):  
Anmol Singh ◽  
Yizhen Zhong ◽  
Layan Nahlawi ◽  
C. Sehwan Park ◽  
Tanima De ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
African Americans ◽  
Genetic Basis ◽  
Critical Role ◽  
Eqtl Analysis ◽  
Biliary Cirrhosis ◽  
Eqtl Mapping ◽  
Genome Wide

Epigenetics is a reversible molecular mechanism that plays a critical role in many developmental, adaptive, and disease processes. DNA methylation has been shown to regulate gene expression and the advent of high throughput technologies has made genome-wide DNA methylation analysis possible. We investigated the effect of DNA methylation in eQTL mapping (methylation-adjusted eQTLs), by incorporating DNA methylation as a SNP-based covariate in eQTL mapping in African American derived hepatocytes. We found that the addition of DNA methylation uncovered new eQTLs and eGenes. Previously discovered eQTLs were significantly altered by the addition of DNA methylation data suggesting that methylation may modulate the association of SNPs to gene expression. We found that methylation-adjusted eQTLs which were less significant compared to PC-adjusted eQTLs were enriched in lipoprotein measurements (FDR = 0.0040), immune system disorders (FDR = 0.0042), and liver enzyme measurements (FDR = 0.047), suggesting a role of DNA methylation in regulating the genetic basis of these phenotypes. Our methylation-adjusted eQTL analysis also uncovered novel SNP-gene pairs. For example, our study found the SNP, rs11546996, was associated to PNKP. In a previous GWAS, this SNP was associated with primary biliary cirrhosis although the causal gene was thought to be SPIB. Our methylation-adjusted method potentially adds new understanding to the genetic basis of complex diseases that disproportionally affect African Americans.

scholarly journals Dynamics of microRNA expression during mouse prenatal development

2018 ◽  
Author(s):  
Sorena Rahmanian ◽  
Rabi Murad ◽  
Alessandra Breschi ◽  
Weihua Zeng ◽  
Mark Mackiewicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Embryonic Development ◽  
Mirna Expression ◽  
Messenger Rna ◽  
Time Course ◽  
Expression Patterns ◽  
Critical Role ◽  
Prenatal Development ◽  
Specific Expression

ABSTRACTMicroRNAs (miRNAs) play a critical role as post-transcriptional regulators of gene expression. The ENCODE project profiled the expression of miRNAs in a comprehensive set of tissues during a time-course of mouse embryonic development and captured the expression dynamics of 785 miRNAs. We found distinct tissue and developmental stage specific miRNA expression clusters, with an overall pattern of increasing tissue specific expression as development proceeds. Comparative analysis of conserved miRNAs in mouse and human revealed stronger clustering of expression patterns by tissue types rather than by species. An analysis of messenger RNA gene expression clusters compared with miRNA expression clusters identifies the potential role of specific miRNA expression clusters in suppressing the expression of mRNAs specific to other developmental programs in the tissue where these microRNAs are expressed during embryonic development. Our results provide the most comprehensive timecourse of miRNA expression as an integrated part of the ENCODE reference dataset for mouse embryonic development.

scholarly journals microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Beibei Liu ◽  
Wei Sun ◽  
Wuyue Gao ◽  
Liqiang Li ◽  
Zhenxue Cao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Dna Methyltransferase ◽  
Cpg Island ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Migration And Invasion ◽  
Differentially Expressed Mirnas ◽  
Cpg Island Methylation

Abstract Background The downregulation of microRNA (miR)-451a has been reported in bladder cancer (BCa) tissues. Herein, we elucidated the role of miR-451a in BCa with the involvement of DNA methyltransferase 3B (DNMT3B). Methods We first screened the differentially expressed miRNAs from the serum of 12 BCa patients and 10 healthy controls in the BCa database GSE113486. Subsequently, we detected miR-451a expression and CpG island methylation of the promoter in BCa cells T24 and 5637 with DNMT3B knockdown. The downstream mRNAs of miR-451a were predicted by bioinformatics and KEGG enrichment analysis. Afterwards, the expression patterns of DNMT3B, miR-451a and erythropoietin-producing hepatocellular receptor tyrosine kinase class A2 (EPHA2) were altered in BCa cells to test the ability of cell proliferation, apoptosis, migration as well as invasion. Finally, the effect of miR-451a and DNMT3B was evaluated in vivo. Results miR-451a was significantly reduced in serum of BCa patients and cell lines. Moreover, the expression of DNMT3B in BCa cells was significantly increased, thus promoting methylation of the miR-451a promoter, resulting in miR-451a inhibition. Additionally, we found that miR-451a targeted and negatively regulated EPHA2, while EPHA2 could activate the PI3K/AKT signaling, driving BCa cell growth and metastasis. Conclusions Our study proposed and demonstrated that miR-451a downregulation mediated by DNMT3B is critical for proliferation, migration, and invasion of BCa, which may be beneficial for developing more effective therapies against BCa.

scholarly journals The critical role of RNA processing and degradation in the control of gene expression

2010 ◽  
Vol 34 (5) ◽  
pp. 883-923 ◽  
Author(s):  
Cecília M. Arraiano ◽  
José M. Andrade ◽  
Susana Domingues ◽  
Inês B. Guinote ◽  
Michal Malecki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Critical Role ◽  
Control Of Gene Expression

Genome-wide investigation of DNA methylation dynamics reveals a critical role of DNA demethylation during the early somatic embryogenesis of Dimocarpus longan Lour

2020 ◽  
Vol 40 (12) ◽  
pp. 1807-1826
Author(s):  
Xiaohui Chen ◽  
Xiaoping Xu ◽  
Xu Shen ◽  
Hansheng Li ◽  
Chen Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Somatic Embryogenesis ◽  
Dna Methyltransferase ◽  
Expression Patterns ◽  
Critical Role ◽  
Dna Demethylation ◽  
Structure Stability ◽  
Dna Hypomethylation ◽  
Dimocarpus Longan

Abstract DNA methylation plays essential roles in gene regulation, chromatin structure stability, gene imprinting, X chromosome inactivation and embryonic development. However, the dynamics and functions of DNA methylation during the early stage of longan (Dimocarpus longan) somatic embryogenesis (SE) are still unclear. In this study, we carried out whole genome bisulphite sequencing and transcriptome sequencing analyses for embryogenic callus (EC), incomplete compact pro-embryogenic cultures (ICpEC) and globular embryos (GE) in an early SE system. At a global level, the DNA 5-methylcytosine content in EC, ICpEC and GE was 24.59, 19.65 and 19.74%, respectively, suggesting a global decrease in DNA methylation from EC to ICpEC and then a slight increase from ICpEC to GE. Differentially methylated region (DMR) analysis showed that hypomethylation mainly occurred in CHH contexts. Gene ontology and Kyoto encyclopedia of genes and genomes analysis of hypomethylated-CHH-DMR-associated genes revealed that zein biosynthesis, fatty acid biosynthesis, circadian rhythm and mitophagy pathways were involved in longan early SE. Expression patterns of DNA methyltransferase and demethylase genes during longan early SE suggested that the decrease in DNA methylation was probably regulated by DNA methyltransferase genes and the DNA demethylase gene REPRESSOR OF SILENCING 1 (ROS1). The correlation between DNA hypomethylation and gene expression revealed that decreased DNA methylation did not cause extensive changes in gene expression during early longan SE and that gene expression may be affected by methylation changes in gene and downstream regions. Inhibiting DNA methylation with 5-azacytidine treatment in EC promoted the formation of GE and enhanced the capability of longan SE. Our results suggest that DNA demethylation has important roles in longan SE development.

Sign in / Sign up

Export Citation Format

Share Document