scholarly journals 8-OxoG in GC-rich Sp1 binding sites enhances gene transcription during adipose tissue development in juvenile mice

2019 ◽  
Author(s):  
Jong Woo Park ◽  
Young In Han ◽  
Tae Min Kim ◽  
Su Cheong Yeom ◽  
Jaeku Kang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Adipose Tissue ◽  
Binding Sites ◽  
Gene Promoter ◽  
Tissue Development ◽  
Promoter Regions ◽  
Dna Lesion ◽  
Estrogen Response ◽  
Adipose Tissue Development

ABSTRACTThe oxidation of guanine to 8-oxoguanine (8-oxoG) is the most common type of oxidative DNA lesion. There is a growing body of evidence indicating that 8-oxoG is not only pre-mutagenic, but also plays an essential role in modulating gene expression along with its cognate repair proteins. In this study, we investigated the relationship between 8-oxoG formed under intrinsic oxidative stress conditions and gene expression in adipose and lung tissues of juvenile mice. We observed that transcriptional activity and the number of active genes were significantly correlated with the distribution of 8-oxoG in gene promoter regions, as determined by reverse-phase liquid chromatography/mass spectrometry (RP-LC/MS), and 8-oxoG and RNA sequencing. Gene regulation by 8-oxoG was not associated with the degree of 8-oxoG formation. Instead, genes with GC-rich transcription factor binding sites in their promoters became more active with increasing 8-oxoG abundance as also demonstrated by specificity protein 1 (Sp1)- and estrogen response element (ERE)-luciferase assays in human embryonic kidney (HEK293T) cells. These results indicate that the occurrence of 8-oxoG in GC-rich Sp1 binding sites is important for gene regulation during adipose tissue development.

scholarly journals 8-OxoG in GC-rich Sp1 binding sites enhances gene transcription in adipose tissue of juvenile mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jong Woo Park ◽  
Young In Han ◽  
Sung Woo Kim ◽  
Tae Min Kim ◽  
Su Cheong Yeom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Adipose Tissue ◽  
Binding Sites ◽  
Gene Promoter ◽  
Promoter Regions ◽  
Dna Lesion ◽  
Estrogen Response ◽  
Adipose Tissue Development ◽  
Specificity Protein

Abstract The oxidation of guanine to 8-oxoguanine (8-oxoG) is the most common type of oxidative DNA lesion. There is a growing body of evidence indicating that 8-oxoG is not only pre-mutagenic, but also plays an essential role in modulating gene expression along with its cognate repair proteins. In this study, we investigated the relationship between 8-oxoG formed under intrinsic oxidative stress conditions and gene expression in adipose and lung tissues of juvenile mice. We observed that transcriptional activity and the number of active genes were significantly correlated with the distribution of 8-oxoG in gene promoter regions, as determined by reverse-phase liquid chromatography/mass spectrometry (RP-LC/MS), and 8-oxoG and RNA sequencing. Gene regulation by 8-oxoG was not associated with the degree of 8-oxoG formation. Instead, genes with GC-rich transcription factor binding sites in their promoters became more active with increasing 8-oxoG abundance as also demonstrated by specificity protein 1 (Sp1)- and estrogen response element (ERE)-luciferase assays in human embryonic kidney (HEK293T) cells. These results indicate that the occurrence of 8-oxoG in GC-rich Sp1 binding sites is important for gene regulation during adipose tissue development.

scholarly journals Nonparametric Tests for Differential Histone Enrichment with ChIP-Seq Data

2015 ◽  
Vol 14s1 ◽  
pp. CIN.S13972 ◽  
Author(s):  
Qian Wu ◽  
Kyoung-Jae Won ◽  
Hongzhe Li
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Binding Sites ◽  
Negative Binomial ◽  
Kernel Smoothing ◽  
Gene Promoter ◽  
Nonparametric Tests ◽  
Promoter Regions ◽  
Experimental Conditions ◽  
Nonparametric Hypothesis Testing

Chromatin immunoprecipitation sequencing (ChIP-seq) is a powerful method for analyzing protein interactions with DNA. It can be applied to identify the binding sites of transcription factors (TFs) and genomic landscape of histone modification marks (HMs). Previous research has largely focused on developing peak-calling procedures to detect the binding sites for TFs. However, these procedures may fail when applied to ChIP-seq data of HMs, which have diffuse signals and multiple local peaks. In addition, it is important to identify genes with differential histone enrichment regions between two experimental conditions, such as different cellular states or different time points. Parametric methods based on Poisson/negative binomial distribution have been proposed to address this differential enrichment problem and most of these methods require biological replications. However, many ChIP-seq data usually have a few or even no replicates. We propose a nonparametric method to identify the genes with differential histone enrichment regions even without replicates. Our method is based on nonparametric hypothesis testing and kernel smoothing in order to capture the spatial differences in histone-enriched profiles. We demonstrate the method using ChIP-seq data on a comparative epigenomic profiling of adipogenesis of murine adipose stromal cells and the Encyclopedia of DNA Elements (ENCODE) ChIP-seq data. Our method identifies many genes with differential H3K27ac histone enrichment profiles at gene promoter regions between proliferating preadipocytes and mature adipocytes in murine 3T3-L1 cells. The test statistics also correlate with the gene expression changes well and are predictive to gene expression changes, indicating that the identified differentially enriched regions are indeed biologically meaningful.

scholarly journals Long non-coding RNAs in regulation of adipogenesis and adipose tissue function

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tiziana Squillaro ◽  
Gianfranco Peluso ◽  
Umberto Galderisi ◽  
Giovanni Di Bernardo
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Drug Targets ◽  
Metabolic Diseases ◽  
Tissue Development ◽  
Cellular Functions ◽  
Adipose Tissue Development ◽  
And Function

Complex interaction between genetics, epigenetics, environment, and nutrition affect the physiological activities of adipose tissues and their dysfunctions, which lead to several metabolic diseases including obesity or type 2 diabetes. Here, adipogenesis appears to be a process characterized by an intricate network that involves many transcription factors and long noncoding RNAs (lncRNAs) that regulate gene expression. LncRNAs are being investigated to determine their contribution to adipose tissue development and function. LncRNAs possess multiple cellular functions, and they regulate chromatin remodeling, along with transcriptional and post-transcriptional events; in this way, they affect gene expression. New investigations have demonstrated the pivotal role of these molecules in modulating white and brown/beige adipogenic tissue development and activity. This review aims to provide an update on the role of lncRNAs in adipogenesis and adipose tissue function to promote identification of new drug targets for treating obesity and related metabolic diseases.

scholarly journals Undernutrition and stage of gestation influence fetal adipose tissue gene expression

2015 ◽  
Vol 54 (3) ◽  
pp. 263-275 ◽  
Author(s):  
Jacqueline M Wallace ◽  
John S Milne ◽  
Raymond P Aitken ◽  
Dale A Redmer ◽  
Lawrence P Reynolds ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Uncoupling Protein ◽  
Tissue Development ◽  
Maternal Undernutrition ◽  
Pat Gene ◽  
Adipose Tissue Development ◽  
And Function ◽  
The Impact

Low birthweight is a risk factor for neonatal mortality and adverse metabolic health, both of which are associated with inadequate prenatal adipose tissue development. In the present study, we investigated the impact of maternal undernutrition on the expression of genes that regulate fetal perirenal adipose tissue (PAT) development and function at gestation days 89 and 130 (term=145 days). Singleton fetuses were taken from adolescent ewes that were either fed control (C) intake to maintain adiposity throughout pregnancy or were undernourished (UN) to maintain conception weight but deplete maternal reserves (n=7/group). Fetal weight was independent of maternal intake at day 89, but by day 130, fetuses from UN dams were 17% lighter and had lower PAT mass that contained fewer unilocular adipocytes. Relative PAT expression ofIGF1,IGF2,IGF2Rand peroxisome proliferator-activated receptor gamma (PPARG) mRNA was lower in UN than in controls, predominantly at day 89. Independent of maternal nutrition, PAT gene expression ofPPARG, glycerol-3-phosphate dehydrogenase, hormone sensitive lipase, leptin, uncoupling protein 1 and prolactin receptor increased, whereasIGF1,IGF2,IGF1RandIGF2Rdecreased between days 89 and 130. Fatty acid synthase and lipoprotein lipase (LPL) mRNAs were not influenced by nutrition or stage of pregnancy. Females had greaterLPLand leptin mRNA than males, andLPL, leptin andPPARGmRNAs were decreased in UN at day 89 in females only. PAT gene expression correlations with PAT mass were stronger at day 89 than they were at day 130. These data suggest that the key genes that regulate adipose tissue development and function are active beginning in mid-gestation, at which point they are sensitive to maternal undernutrition: this leads to reduced fetal adiposity by late pregnancy.

scholarly journals Cis-regulatory divergence in gene expression between two thermally divergent yeast species

2016 ◽  
Author(s):  
Xueying C. Li ◽  
Justin C. Fay
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Binding Sites ◽  
Small Subset ◽  
Regulatory Sequences ◽  
Promoter Regions ◽  
Specific Expression ◽  
Thermal Growth ◽  
Allele Specific ◽  
Regulatory Effects

AbstractGene regulation is a ubiquitous mechanism by which organisms respond to their environment. While organisms are often found to be adapted to the environments they experience, the role of gene regulation in environmental adaptation is not often known. In this study, we examine divergence in cis-regulatory effects between two Saccharomyces species, S. cerevisiae and S. uvarum, that have substantially diverged in their thermal growth profile. We measured allele specific expression (ASE) in the species’ hybrid at three temperatures, the highest of which is lethal to S. uvarum but not the hybrid or S. cerevisiae. We find that S. uvarum alleles can be expressed at the same level as S. cerevisiae alleles at high temperature and most cis-acting differences in gene expression are not dependent on temperature. While a small set of 136 genes show temperature-dependent ASE, we find no indication that signatures of directional cis-regulatory evolution are associated with temperature. Within promoter regions we find binding sites enriched upstream of temperature responsive genes, but only weak correlations between binding site and expression divergence. Our results indicate that temperature divergence between S. cerevisiae and S. uvarum has not caused widespread divergence in cis-regulatory activity, but point to a small subset of genes where the species’ alleles show differences in magnitude or opposite responses to temperature. The difficulty of explaining divergence in cis-regulatory sequences with models of transcription factor binding sites and nucleosome positioning highlights the importance of identifying mutations that underlie cis-regulatory divergence between species.

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