scholarly journals Identification of a 5-Methylcytosine Site that may Regulate C/EBPβ Binding and Determine Tissue-Specific Expression of the BPI Gene in Piglets

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Li Sun ◽  
Jing Wang ◽  
Xuemei Yin ◽  
Shouyong Sun ◽  
Chen Zi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Tissue Specificity ◽  
Cpg Islands ◽  
Immune Defense ◽  
Mrna Levels ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Promoter Dna

Abstract Bactericidal/permeability-increasing protein (BPI) plays an important role in innate immune defense in mammals. A previous study showed that BPI gene expression correlates to gram-negative bacteria resistance. However, this gene showed tissue-specific expression in piglets and strongly expressed only in the digestive tract. To investigate the mechanisms governing the tissue-specificity, bisulfite sequencing PCR and next generation sequencing were used for high accuracy methylation quantitation of CpG islands of BPI gene upstream in 11 different tissues from weaned Yorkshire piglets. Additionally, qPCR was used to examine mRNA levels of BPI gene as well as transcription factor. We additionally analyzed transcriptional regulation by studying key 5-methylcytosine sites and transcription factors. Results showed that BPI mRNA levels significantly correlated with the overall methylation as well as methylation at mC-15 which was non-CpG site, no significant correlation could be found between the BPI and transcription factor mRNA levels, EMSA test showed that C/EBPβ could interact with BPI wild-type promoter DNA, but not methylated DNA. So we confirmed that methylation of mC-15 residue could inhibit the ability of C/EBPβ binding to the BPI promoter and affect the expression, and this mechanism probably plays a role in the tissue specificity of BPI gene expression in weaned piglets.

scholarly journals HNF1alpha is involved in tissue-specific regulation of CFTR gene expression

2004 ◽  
Vol 378 (3) ◽  
pp. 909-918 ◽  
Author(s):  
Nathalie MOUCHEL ◽  
Sytse A. HENSTRA ◽  
Victoria A. McCARTHY ◽  
Sarah H. WILLIAMS ◽  
Marios PHYLACTIDES ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Tissue Specificity ◽  
Regulatory Elements ◽  
Upstream Region ◽  
Mrna Levels ◽  
Tissue Specific ◽  
Specific Regulation

The CFTR (cystic fibrosis transmembrane conductance regulator) gene shows a complex pattern of expression with tissue-specific and temporal regulation. However, the genetic elements and transcription factors that control CFTR expression are largely unidentified. The CFTR promoter does not confer tissue specificity on gene expression, suggesting that there are regulatory elements outside the upstream region. Analysis of potential regulatory elements defined as DNase 1-hypersensitive sites within introns of the gene revealed multiple predicted binding sites for the HNF1α (hepatocyte nuclear factor 1α) transcription factor. HNF1α, which is expressed in many of the same epithelial cell types as CFTR and shows similar differentiation-dependent changes in gene expression, bound to these sites in vitro. Overexpression of heterologous HNF1α augmented CFTR transcription in vivo. In contrast, antisense inhibition of HNF1α transcription decreased the CFTR mRNA levels. Hnf1α knockout mice showed lower levels of CFTR mRNA in their small intestine in comparison with wild-type mice. This is the first report of a transcription factor, which confers tissue specificity on the expression of this important disease-associated gene.

scholarly journals Methylation of the Cyclin A1 Promoter Correlates with Gene Silencing in Somatic Cell Lines, while Tissue-Specific Expression of Cyclin A1 Is Methylation Independent

2000 ◽  
Vol 20 (9) ◽  
pp. 3316-3329 ◽  
Author(s):  
Carsten Müller ◽  
Carol Readhead ◽  
Sven Diederichs ◽  
Gregory Idos ◽  
Rong Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Promoter Methylation ◽  
Cpg Island ◽  
Trichostatin A ◽  
Specific Gene ◽  
Cyclin A1 ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

ABSTRACT Gene expression in mammalian organisms is regulated at multiple levels, including DNA accessibility for transcription factors and chromatin structure. Methylation of CpG dinucleotides is thought to be involved in imprinting and in the pathogenesis of cancer. However, the relevance of methylation for directing tissue-specific gene expression is highly controversial. The cyclin A1 gene is expressed in very few tissues, with high levels restricted to spermatogenesis and leukemic blasts. Here, we show that methylation of the CpG island of the human cyclin A1 promoter was correlated with nonexpression in cell lines, and the methyl-CpG binding protein MeCP2 suppressed transcription from the methylated cyclin A1 promoter. Repression could be relieved by trichostatin A. Silencing of a cyclin A1 promoter-enhanced green fluorescent protein (EGFP) transgene in stable transfected MG63 osteosarcoma cells was also closely associated with de novo promoter methylation. Cyclin A1 could be strongly induced in nonexpressing cell lines by trichostatin A but not by 5-aza-cytidine. The cyclin A1 promoter-EGFP construct directed tissue-specific expression in male germ cells of transgenic mice. Expression in the testes of these mice was independent of promoter methylation, and even strong promoter methylation did not suppress promoter activity. MeCP2 expression was notably absent in EGFP-expressing cells. Transcription from the transgenic cyclin A1 promoter was repressed in most organs outside the testis, even when the promoter was not methylated. These data show the association of methylation with silencing of the cyclin A1 gene in cancer cell lines. However, appropriate tissue-specific repression of the cyclin A1 promoter occurs independently of CpG methylation.

scholarly journals Human acyl-CoA:cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma

2006 ◽  
Vol 394 (3) ◽  
pp. 617-626 ◽  
Author(s):  
Bao-Liang Song ◽  
Can-Hua Wang ◽  
Xiao-Min Yao ◽  
Li Yang ◽  
Wen-Jing Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Molecular Mechanism ◽  
Luciferase Reporter ◽  
Hepatoma Cell Line ◽  
Cis Elements ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Cdx2 Expression

Humans express two ACAT (acyl-CoA:cholesterol acyltransferase) genes, ACAT1 and ACAT2. ACAT1 is ubiquitously expressed, whereas ACAT2 is primarily expressed in intestinal mucosa and plays an important role in intestinal cholesterol absorption. To investigate the molecular mechanism(s) responsible for the tissue-specific expression of ACAT2, we identified five cis-elements within the human ACAT2 promoter, four for the intestinal-specific transcription factor CDX2 (caudal type homeobox transcription factor 2), and one for the transcription factor HNF1α (hepatocyte nuclear factor 1α). Results of luciferase reporter and electrophoretic mobility shift assays show that CDX2 and HNF1α exert a synergistic effect, enhancing the ACAT2 promoter activity through binding to these cis-elements. In undifferentiated Caco-2 cells, the ACAT2 expression is increased when exogenous CDX2 and/or HNF1α are expressed by co-transfection. In differentiated Caco-2 cells, the ACAT2 expression significantly decreases when the endogenous CDX2 or HNF1α expression is suppressed by using RNAi (RNA interference) technology. The expression levels of CDX2, HNF1α, and ACAT2 are all greatly increased when the Caco-2 cells differentiate to become intestinal-like cells. These results provide a molecular mechanism for the tissue-specific expression of ACAT2 in intestine. In normal adult human liver, CDX2 expression is not detectable and the ACAT2 expression is very low. In the hepatoma cell line HepG2 the CDX2 expression is elevated, accounting for its elevated ACAT2 expression. A high percentage (seven of fourteen) of liver samples from patients affected with hepatocellular carcinoma exhibited elevated ACAT2 expression. Thus, the elevated ACAT2 expression may serve as a new biomarker for certain form(s) of hepatocellular carcinoma.

scholarly journals Predicting tissue-specific gene expression from whole blood transcriptome

2020 ◽  
Author(s):  
Mahashweta Basu ◽  
Kun Wang ◽  
Eytan Ruppin ◽  
Sridhar Hannenhalli
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Specific Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Complex Disorders ◽  
Tissue Specific Gene ◽  
Tissue Specific Expression ◽  
Specific Gene Expression ◽  
Blood Transcriptome

AbstractComplex diseases are systemic, largely mediated via transcriptional dysregulation in multiple tissues. Thus, knowledge of tissue-specific transcriptome in an individual can provide important information about an individual’s health. Unfortunately, with a few exceptions such as blood, skin, and muscle, an individual’s tissue-specific transcriptome is not accessible through non-invasive means. However, due to shared genetics and regulatory programs between tissues, the transcriptome in blood may be predictive of those in other tissues, at least to some extent. Here, based on GTEx data, we address this question in a rigorous, systematic manner, for the first time. We find that an individual’s whole blood gene expression and splicing profile can predict tissue-specific expression levels in a significant manner (beyond demographic variables) for many genes. On average, across 32 tissues, the expression of about 60% of the genes is predictable from blood expression in a significant manner, with a maximum of 81% of the genes for the musculoskeletal tissue. Remarkably, the tissue-specific expression inferred from the blood transcriptome is almost as good as the actual measured tissue expression in predicting disease state for six different complex disorders, including Hypertension and Type 2 diabetes, substantially surpassing predictors built directly from the blood transcriptome. The code for our pipeline for tissue-specific gene expression prediction – TEEBoT, is provided, enabling others to study its potential translational value in other indications.

scholarly journals Identification of key tissue-specific, biological processes by integrating enhancer information in maize gene regulatory networks

2020 ◽  
Author(s):  
Maud Fagny ◽  
Marieke Lydia Kuijjer ◽  
Maike Stam ◽  
Johann Joets ◽  
Olivier Turc ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Binding Sites ◽  
Regulatory Network ◽  
Tissue Specificity ◽  
Target Genes ◽  
Specific Gene ◽  
Tissue Specific ◽  
Genome Wide ◽  
Gene Regulatory

AbstractEnhancers are important regulators of gene expression during numerous crucial processes including tissue differentiation across development. In plants, their recent molecular characterization revealed their capacity to activate the expression of several target genes through the binding of transcription factors. Nevertheless, identifying these target genes at a genome-wide level remains a challenge, in particular in species with large genomes, where enhancers and target genes can be hundreds of kilobases away. Therefore, the contribution of enhancers to regulatory network is still poorly understood in plants. In this study, we investigate the enhancer-driven regulatory network of two maize tissues at different stages: leaves at seedling stage and husks (bracts) at flowering. Using a systems biology approach, we integrate genomic, epigenomic and transcriptomic data to model the regulatory relationship between transcription factors and their potential target genes. We identify regulatory modules specific to husk and V2-IST, and show that they are involved in distinct functions related to the biology of each tissue. We evidence enhancers exhibiting binding sites for two distinct transcription factor families (DOF and AP2/ERF) that drive the tissue-specificity of gene expression in seedling immature leaf and husk. Analysis of the corresponding enhancer sequences reveals that two different transposable element families (TIR transposon Mutator and MITE Pif/Harbinger) have shaped the regulatory network in each tissue, and that MITEs have provided new transcription factor binding sites that are involved in husk tissue-specificity.SignificanceEnhancers play a major role in regulating tissue-specific gene expression in higher eukaryotes, including angiosperms. While molecular characterization of enhancers has improved over the past years, identifying their target genes at the genome-wide scale remains challenging. Here, we integrate genomic, epigenomic and transcriptomic data to decipher the tissue-specific gene regulatory network controlled by enhancers at two different stages of maize leaf development. Using a systems biology approach, we identify transcription factor families regulating gene tissue-specific expression in husk and seedling leaves, and characterize the enhancers likely to be involved. We show that a large part of maize enhancers is derived from transposable elements, which can provide novel transcription factor binding sites crucial to the regulation of tissue-specific biological functions.

CpG islands in genes showing tissue-specific expression

1990 ◽  
Vol 326 (1235) ◽  
pp. 207-215 ◽  
Keyword(s):  
Gene Expression ◽  
Cpg Islands ◽  
Housekeeping Genes ◽  
Tissue Expression ◽  
Proximal Promoter ◽  
Cell Type ◽  
Promoter Regions ◽  
Specific Expression ◽  
Tissue Specific ◽  
Single Cell Type

Patterns of DNA methylation at GpG dinucleotides and their relations with gene expression are complex. Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences. However, in the human carbonic anhydrase (CA) gene family, both the ubiquitously expressed CAII and the muscle specific CAIII appear to have such CpG islands although erythrocyte-specific CAI does not. The CAII island is quantitatively more CpG rich than that of CAIII, with a CpG :GpC ratio of 0.94 compared with 0.82 for CAIII. Estimation of CpG:GpC ratios in the proximal-promoter regions of 44 vertebrate genes suggest that 40% of genes with tissue-specific or limited tissue distribution may show methylation-free CpG clusters in their promoter regions. In many cases the CpG:GpC ratio is less than that found in housekeeping genes and this may reflect variation in the interaction of CpG clusters with regulatory factors that define different patterns of tissue expression.

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