scholarly journals Correlation between miRNA-targeting-specific promotermethylation and miRNA regulation of target genes

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 21
Author(s):  
Y-h Taguchi
Keyword(s):  
Gene Expression ◽  
Promoter Methylation ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Gene Expression Omnibus ◽  
Mirna Regulation ◽  
P Values ◽  
Regulate Gene Expression ◽  
Mirna Targeting ◽  
Regulate Gene

Background miRNA regulation of target genes and promoter methylation were known to be the primary mechanisms underlying the epigenetic regulation of gene expression. However, how these two processes cooperatively regulate gene expression has not been extensively studied. Methods Gene expression and promoter methylation profiles of 271 distinct human cell lines were obtained from gene expression omnibus. P-values that describe both miRNA-targeting-specific promoter methylation and miRNA regulation of target genes were computed with the MiRaGE method proposed recently by the author. Results We found that promoter methylation was miRNA-targeting-specific. In other words, changes in promoter methylation were associated with miRNA binding at target genes. It was also found that miRNA-targeting-specific promoter hypomethylation was related to miRNA regulation; the genes with miRNA-targeting-specific promoter hypomethylation were downregulated during cell senescence and upregulated during cellulardierentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, and primate-specific miRNAs that are typically expressed at lower levels than the frequently investigated conserved miRNAs. Conclusions It was found that promoter methylation was affected by miRNA targeting. Furthermore, miRNA-targeting-specific promoter hypomethylation was suggested to facilitate gene regulation by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs).

scholarly journals Correlation between miRNA-targeted-gene promoter methylation and miRNA regulation of target genes

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 21 ◽  
Author(s):  
Y-h Taguchi
Keyword(s):  
Gene Expression ◽  
Promoter Methylation ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Gene Promoter ◽  
Gene Expression Omnibus ◽  
Seed Region ◽  
Mirna Regulation ◽  
Regulate Gene Expression ◽  
Mirna Targeting

Background miRNA regulation of target genes and promoter methylation are known to be the primary mechanisms underlying the epigenetic regulation of gene expression. However, how these two processes cooperatively regulate gene expression has not been extensively studied.Methods Gene expression and promoter methylation profiles of 270 distinct human cell lines were obtained from Gene Expression Omnibus. P-values that describe both miRNA-targeted-gene promoter methylation and miRNA regulation of target genes were computed using the MiRaGE method proposed recently by the author.Results Significant changes in promoter methylation were associated with miRNA targeting. It was also found that miRNA-targeted-gene promoter hypomethylation was related to differential target gene expression; the genes with miRNA-targeted-gene promoter hypomethylation were downregulated during cell senescence and upregulated during cellular differentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, primate-specific miRNAs that are typically expressed at lower levels than the frequently investigated conserved miRNAs. miRNA-targeted-gene promoter methylation may also be related to the seed region features of miRNA.Conclusions It was found that promoter methylation was correlated to miRNA targeting. Furthermore, miRNA-targeted-gene promoter hypomethylation was especially enhanced in promoters of genes targeted by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs) and was suggested to be highly related to some seed region features of miRNAs.

scholarly journals Correlation between miRNA-targeted-gene promoter methylation and miRNA regulation of target genes

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 21 ◽  
Author(s):  
Y-h Taguchi
Keyword(s):  
Gene Expression ◽  
Promoter Methylation ◽  
Target Gene ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Gene Promoter ◽  
Gene Expression Omnibus ◽  
Mirna Regulation ◽  
Regulate Gene Expression ◽  
Mirna Targeting

Background miRNA regulation of target genes and promoter methylation are known to be the primary mechanisms underlying the epigenetic regulation of gene expression. However, how these two processes cooperatively regulate gene expression has not been extensively studied. Methods Gene expression and promoter methylation profiles of 271 distinct human cell lines were obtained from gene expression omnibus. P-values that describe both miRNA-targeted-gene promoter methylaion and miRNA regulation of target genes were computed using the MiRaGE method proposed recently by the author.Results Significant changes in promoter methylation were associated with miRNA targeting. It was also found that miRNA-targeted-gene promoter hypomethylation was related to differential target gene expression; the genes with miRNA-targeted-gene promoter hypomethylation were downregulated during cell senescence and upregulated during cellular differentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, primate-specific miRNAs that are typically expressed at lower levels than the frequently investigated conserved miRNAs.Conclusions It was found that promoter methylation was affected by miRNA targeting. Furthermore, miRNA-targeted-gene promoter hypomethylation is suggested to facilitate gene regulation by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs).

scholarly journals Polyamines regulate gene expression by stimulating translation of histone acetyltransferase mRNAs

2020 ◽  
Vol 295 (26) ◽  
pp. 8736-8745 ◽  
Author(s):  
Akihiko Sakamoto ◽  
Yusuke Terui ◽  
Takeshi Uemura ◽  
Kazuei Igarashi ◽  
Keiko Kashiwagi
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Histone Acetyltransferases ◽  
Regulate Gene Expression ◽  
Double Stranded Rna ◽  
Protein Levels ◽  
Lysine Residues ◽  
Regulate Gene ◽  
Stimulation Of

Polyamines regulate gene expression in Escherichia coli by translationally stimulating mRNAs encoding global transcription factors. In this study, we focused on histone acetylation, one of the mechanisms of epigenetic regulation of gene expression, to attempt to clarify the role of polyamines in the regulation of gene expression in eukaryotes. We found that activities of histone acetyltransferases in both the nucleus and cytoplasm decreased significantly in polyamine-reduced mouse mammary carcinoma FM3A cells. Although protein levels of histones H3 and H4 did not change in control and polyamine-reduced cells, acetylation of histones H3 and H4 was greatly decreased in the polyamine-reduced cells. Next, we used control and polyamine-reduced cells to identify histone acetyltransferases whose synthesis is stimulated by polyamines. We found that polyamines stimulate the translation of histone acetyltransferases GCN5 and HAT1. Accordingly, GCN5- and HAT1-catalyzed acetylation of specific lysine residues on histones H3 and H4 was stimulated by polyamines. Consistent with these findings, transcription of genes required for cell proliferation was enhanced by polyamines. These results indicate that polyamines regulate gene expression by enhancing the expression of the histone acetyltransferases GCN5 and HAT1 at the level of translation. Mechanistically, polyamines enhanced the interaction of microRNA-7648-5p (miR-7648-5p) with the 5′-UTR of GCN5 mRNA, resulting in stimulation of translation due to the destabilization of the double-stranded RNA (dsRNA) between the 5′-UTR and the ORF of GCN5 mRNA. Because HAT1 mRNA has a short 5′-UTR, polyamines may enhance initiation complex formation directly on this mRNA.

scholarly journals An Evolutionary Perspective of Animal MicroRNAs and Their Targets

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Noam Shomron ◽  
David Golan ◽  
Eran Hornstein
Keyword(s):  
Gene Expression ◽  
Posttranscriptional Regulation ◽  
Noncoding Rnas ◽  
Mrna Degradation ◽  
Evolutionary Perspective ◽  
Mirna Regulation ◽  
Regulate Gene Expression ◽  
Mirna Genes ◽  
Genomic Architecture ◽  
Regulate Gene

MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression through translational inhibition or mRNA degradation by binding to sequences on the target mRNA. miRNA regulation appears to be the most abundant mode of posttranscriptional regulation affecting 50% of the transcriptome. miRNA genes are often clustered and/or located in introns, and each targets a variable and often large number of mRNAs. Here we discuss the genomic architecture of animal miRNA genes and their evolving interaction with their target mRNAs.

scholarly journals H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions

2019 ◽  
Author(s):  
Yichao Cai ◽  
Ying Zhang ◽  
Yan Ping Loh ◽  
Jia Qi Tng ◽  
Mei Chee Lim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Target Genes ◽  
Gene Repression ◽  
Xenograft Tumor ◽  
Regulate Gene Expression ◽  
Chromatin Interactions ◽  
Genomic Regions ◽  
Xenograft Tumor Growth ◽  
Regulate Gene

AbstractGene repression and silencers are poorly understood. We reasoned that H3K27me3-rich regions (MRRs) of the genome defined from clusters of H3K27me3 peaks may be used to identify silencers that can regulate gene expression via proximity or looping. MRRs were associated with chromatin interactions and interact preferentially with each other. MRR component removal at interaction anchors by CRISPR led to upregulation of interacting target genes, altered H3K27me3 and H3K27ac levels at interacting regions, and altered chromatin interactions. Chromatin interactions did not change at regions with high H3K27me3, but regions with low H3K27me3 and high H3K27ac levels showed changes in chromatin interactions. The MRR knockout cells also showed changes in phenotype associated with cell identity, and altered xenograft tumor growth. MRR-associated genes and long-range chromatin interactions were susceptible to H3K27me3 depletion. Our results characterized H3K27me3-rich regions and their mechanisms of functioning via looping.

scholarly journals Bases of antisense IncRNA-associated regulation of gene expression in fission yeast

2017 ◽  
Author(s):  
Maxime Wery ◽  
Camille Gautier ◽  
Marc Descrimes ◽  
Mayuko Yoda ◽  
Valérie Migeot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Fission Yeast ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Model Organisms ◽  
Critical Threshold ◽  
Multiple Model ◽  
Regulate Gene Expression ◽  
Regulate Gene

ABSTRACTAntisense (as)lncRNAs can regulate gene expression but the underlying mechanisms and the different cofactors involved remain unclear. Using Native Elongating Transcript sequencing, here we show that stabilization of antisense Exo2-sensitivite IncRNAs (XUTs) results in the attenuation, at the nascent transcription level, of a subset of highly expressed genes displaying prominent promoter-proximal nucleosome depletion and histone acetylation. Mechanistic investigations on the catalase genectt1revealed that its induction following oxidative stress is impaired in Exo2-deficient cells, correlating with the accumulation of an asXUT. Interestingly, expression of this asXUT was also activated in wild-type cells upon oxidative stress, concomitant toctt1induction, indicating a potential attenuation feedback. This attenuation correlates with asXUT abundance, it is transcriptional, characterized by low RNAPII-ser5 phosphorylation, and it requires an histone deacetylase activity and the conserved Set2 histone methyltransferase. Finally, we identified Dicer as another RNA processing factor acting onctt1induction, but independently of Exo2. We propose that asXUTs could modulate the expression of their paired-sense genes when it exceeds a critical threshold, using a conserved mechanism independent of RNAi.AUTHOR SUMMARYExamples of regulatory antisense (as)lncRNAs acting on gene expression have been reported in multiple model organisms. However, despite their regulatory importance, aslncRNAs have been poorly studied, and the molecular bases for aslncRNAs-mediated regulation remain incomplete. One reason for the lack of global information on aslncRNAs appears to be their low cellular abundance. Indeed, our previous studies in budding and fission yeasts revealed that aslncRNAs are actively degraded by the Xrn1/Exo2-dependent cytoplasmic 5′-3′ RNA decay pathway. Using a combination of single-gene and genome-wide analyses in fission yeast, here we report that the stabilization of a set of Exo2-sensitive aslncRNAs correlates with attenuation of paired-sense genes transcription. Our work provides fundamental insights into the mechanism by which aslncRNAs could regulate gene expression. It also highlights for the first time that the level of sense gene transcription and the presence of specific chromatin features could define the potential of aslncRNA-mediated attenuation, raising the idea that aslncRNAs only attenuate those genes with expression levels above a “regulatory threshold”. This opens novel perspectives regarding what the potential determinants of aslncRNA-dependent regulation, as previous models in budding yeast rather proposed that aslncRNA-mediated repression is restricted to lowly expressed genes.

scholarly journals Epigenetics on the brain: Modifying chromatin and behaviour

2010 ◽  
Vol 32 (5) ◽  
pp. 18-20
Author(s):  
Mary G. Goll
Keyword(s):  
Gene Expression ◽  
Cell Division ◽  
Epigenetic Regulation ◽  
Normal Development ◽  
Regulation Of Gene Expression ◽  
Regulate Gene Expression ◽  
Neuropsychiatric Disease ◽  
The Brain ◽  
Regulate Gene

Proper regulation of gene expression is essential for the development and survival of every organ ism. Epigenetic modifications provide a way for cells to regulate gene expression and to propagate expression states heritably through cell division. Given the brain's complexity, it is not surprising that epigenetic regulation is essential for both normal development and maintenance of homoeostasis of this organ. New data suggest that the role of epigenetic regulation in the brain may extend much further, influencing both the ways neurons organize their networks in response to new experiences and the resultant behaviours. Such studies highlight the relevance of epigenetic regulation for neu rodevelopmental and neuropsychiatric disease.

scholarly journals Whole genome 6-methyladenosine sequencing (6-mA-Seq) enables bacterial epigenomics studies

2021 ◽  
Author(s):  
Rachel R. Spurbeck ◽  
Angela T. Minard-Smith ◽  
Lindsay A. Catlin ◽  
Robert W. Murdoch ◽  
Rich M. Chou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bisulfite Sequencing ◽  
Regulation Of Gene Expression ◽  
Carbon Sources ◽  
Carbon Utilization ◽  
Regulate Gene Expression ◽  
Bisulfite Treatment ◽  
Methylation Patterns ◽  
Epigenetic Research ◽  
Regulate Gene

AbstractMethylation sequencing using bisulfite treatment has revolutionized the field of molecular biology for eukaryotic systems, unveiling levels of intricacy in regulation of gene expression in response to different environmental conditions. While bacteria also utilize methylation to regulate gene expression, bisulfite sequencing does not work as well in bacteria as in eukaryotes, because bacteria methylate adenosine instead of cytosine. Therefore, global bacterial methylation patterns cannot be studied using common Illumina sequencers. In this work, we demonstrate 6mA-seq, a method that can be used to identify patterns in bacteria that methylate adenosines at GATC sites. Furthermore, this method was used on Escherichia coli cultured on four different carbon sources to demonstrate different methylation patterns due to carbon utilization. 6mA-seq can increase the speed in which epigenetic research is conducted in bacteria.

Epigenetic regulation mechanisms of microRNA expression

2017 ◽  
Vol 8 (5-6) ◽  
pp. 203-212 ◽  
Author(s):  
Sara Morales ◽  
Mariano Monzo ◽  
Alfons Navarro
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Proliferation ◽  
Epigenetic Regulation ◽  
Regulation Of Gene Expression ◽  
Transcriptional Level ◽  
Regulate Gene Expression ◽  
Regulation Mechanisms ◽  
Regulate Gene

AbstractMicroRNAs (miRNAs) are single-stranded RNAs of 18–25 nucleotides that regulate gene expression at the post-transcriptional level. They are involved in many physiological and pathological processes, including cell proliferation, apoptosis, development and carcinogenesis. Because of the central role of miRNAs in the regulation of gene expression, their expression needs to be tightly controlled. Here, we summarize the different mechanisms of epigenetic regulation of miRNAs, with a particular focus on DNA methylation and histone modification.

scholarly journals Zinc finger protein SALL4 functions through an AT-rich motif to regulate gene expression

2020 ◽  
Author(s):  
Nikki R. Kong ◽  
Mahmoud A. Bassal ◽  
Hong Kee Tan ◽  
Jesse V. Kurland ◽  
Kol Jia Yong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Cancer Cells ◽  
Zinc Finger ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Embryonic Stem ◽  
Regulate Gene Expression ◽  
Protein Binding Microarray ◽  
Regulate Gene

SummaryThe zinc finger transcription factor SALL4 is highly expressed in embryonic stem cells, down-regulated in most adult tissues, but reactivated in many aggressive cancers. This unique expression pattern makes SALL4 an attractive target for designing therapeutic strategies. However, whether SALL4 binds DNA directly to regulate gene expression is unclear and many of its targets in cancer cells remain elusive. Here, through an unbiased screen of protein binding microarray (PBM) and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) experiments, we identified and validated the DNA binding domain of SALL4 and its consensus binding sequence. Combined with RNA-seq analyses after SALL4 knockdown, we discovered hundreds of new SALL4 target genes that it directly regulates in aggressive liver cancer cells, including genes encoding a family of Histone 3 Lysine 9-specific Demethylases (KDMs). Taken together, these results elucidated the mechanism of SALL4 DNA binding and revealed novel pathways and molecules to target in SALL4-dependent tumors.

Sign in / Sign up

Export Citation Format

Share Document