Progesterone is primary regulator of Cdk2ap1 gene expression and tissue-specific expression in the uterus

2010 ◽  
Vol 33 (9) ◽  
pp. 650-656
Author(s):  
Y. P. Cheon ◽  
C. H. Kim
Keyword(s):  
Gene Expression ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

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 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 GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland.

1994 ◽  
Vol 14 (8) ◽  
pp. 5592-5602 ◽  
Author(s):  
D J Steger ◽  
J H Hecht ◽  
P L Mellon
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Alpha Subunit ◽  
Sequence Motif ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Specific Expression ◽  
Tissue Specific ◽  
Response Elements ◽  
Tissue Specific Expression

The human glycoprotein hormone alpha-subunit gene is expressed in two quite dissimilar tissues, the placenta and anterior pituitary. Tissue-specific expression is determined by combinations of elements, some of which are common and others of which are specific to each tissue. In the placenta, a composite enhancer confers specific expression. It contains four protein-binding sites: two cyclic AMP (cAMP) response elements that bind CREB, a trophoblast-specific element that binds TSEB, and a sequence motif, AGATAA, that matches the consensus binding site for a family of transcription factors termed the GATA-binding proteins. In pituitary gonadotropes, the cAMP response elements remain important for expression, TSEB is absent, and elements further upstream participate in tissue-specific expression. Here we establish a regulatory role for the GATA element in both the placenta and pituitary by demonstrating that a mutation of this element decreases alpha-subunit gene expression 15-fold in JEG-3 human placental cells and 2.5-fold in alpha T3-1 mouse pituitary gonadotropes. In JEG-3 cells, human GATA-2 (hGATA-2) and hGATA-3 are highly expressed and both proteins bind to the alpha-subunit gene GATA element. In alpha T3-1 cells, the GATA motif is bound by mouse GATA-2 (mGATA-2) and an mGATA-4-related protein. Cotransfection of hGATA-2 or hGATA-3 into alpha T3-1 cells activates the alpha-subunit gene threefold. These studies establish a role for the GATA-binding proteins in placental and pituitary alpha-subunit gene expression, significantly expanding the known target genes of GATA-2, GATA-3, and perhaps GATA-4.

scholarly journals LDexpress: an online tool for integrating population-specific linkage disequilibrium patterns with tissue-specific expression data

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shu-Hong Lin ◽  
Rohit Thakur ◽  
Mitchell J. Machiela
Keyword(s):  
Gene Expression ◽  
Linkage Disequilibrium ◽  
Genetic Susceptibility ◽  
Genome Wide Association Studies ◽  
Expression Data ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Wide Range ◽  
Germline Variation

AbstractGenome-wide association studies have identified thousands of genetic susceptibility loci associated with cancer as well as other traits and diseases. Mapping germline variation in identified genetic susceptibility regions to alterations in nearby gene expression nominates candidate genes potentially related to disease risk for further functional investigation. We developed LDexpress as an online resource that integrates population-specific linkage disequilibrium data from the 1000 Genomes (1000G) project and tissue-specific expression data from the Genotype-Tissue Expression project to better study regional germline variation impacting gene expression. LDexpress is a publicly available web tool designed to be easy to use, flexible to conduct a wide range of variant queries, and quick to efficiently investigate dozens of query variants across multiple tissue types. We demonstrate the utility of LDexpress using example genomic queries and anticipate this tool will accelerate understanding of disease etiology by uncovering associations of regional germline variation to nearby gene expression.

scholarly journals Mouse and Human BAC Transgenes Recapitulate Tissue-Specific Expression of the Vitamin D Receptor in Mice and Rescue the VDR-Null Phenotype

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2064-2076 ◽  
Author(s):  
Seong Min Lee ◽  
Kathleen A. Bishop ◽  
Joseph J. Goellner ◽  
Charles A. O'Brien ◽  
J. Wesley Pike
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Null Mouse ◽  
Vdr Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Artificial Chromosomes ◽  
Tissue Specific Expression

The biological actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by the vitamin D receptor (VDR), which is expressed in numerous target tissues in a cell type-selective manner. Recent studies using genomic analyses and recombineered bacterial artificial chromosomes (BACs) have defined the specific features of mouse and human VDR gene loci in vitro. In the current study, we introduced recombineered mouse and human VDR BACs as transgenes into mice and explored their expression capabilities in vivo. Individual transgenic mouse strains selectively expressed BAC-derived mouse or human VDR proteins in appropriate vitamin D target tissues, thereby recapitulating the tissue-specific expression of endogenous mouse VDR. The mouse VDR transgene was also regulated by 1,25(OH)2D3 and dibutyryl-cAMP. When crossed into a VDR-null mouse background, both transgenes restored wild-type basal as well as 1,25(OH)2D3-inducible gene expression patterns in the appropriate tissues. This maneuver resulted in the complete rescue of the aberrant phenotype noted in the VDR-null mouse, including systemic features associated with altered calcium and phosphorus homeostasis and disrupted production of parathyroid hormone and fibroblast growth factor 23, and abnormalities associated with the skeleton, kidney, parathyroid gland, and the skin. This study suggests that both mouse and human VDR transgenes are capable of recapitulating basal and regulated expression of the VDR in the appropriate mouse tissues and restore 1,25(OH)2D3 function. These results provide a baseline for further dissection of mechanisms integral to mouse and human VDR gene expression and offer the potential to explore the consequence of selective mutations in VDR proteins in vivo.

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

2021 ◽  
Vol 7 (14) ◽  
pp. eabd6991
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

Complex diseases are mediated via transcriptional dysregulation in multiple tissues. Thus, knowing an individual’s tissue-specific gene expression can provide critical information about her health. Unfortunately, for most tissues, the transcriptome cannot be obtained without invasive procedures. Could we, however, infer an individual’s tissue-specific expression from her whole blood transcriptome? Here, we rigorously address this question. We find that an individual’s whole blood transcriptome can significantly predict tissue-specific expression levels for ~60% of the genes on average across 32 tissues, with up to 81% of the genes in skeletal muscle. 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 the blood transcriptome. The code for tissue-specific gene expression prediction, TEEBoT, is provided, enabling others to study its potential translational value in other indications.

GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland

1994 ◽  
Vol 14 (8) ◽  
pp. 5592-5602
Author(s):  
D J Steger ◽  
J H Hecht ◽  
P L Mellon
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Alpha Subunit ◽  
Sequence Motif ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Specific Expression ◽  
Tissue Specific ◽  
Response Elements ◽  
Tissue Specific Expression

The human glycoprotein hormone alpha-subunit gene is expressed in two quite dissimilar tissues, the placenta and anterior pituitary. Tissue-specific expression is determined by combinations of elements, some of which are common and others of which are specific to each tissue. In the placenta, a composite enhancer confers specific expression. It contains four protein-binding sites: two cyclic AMP (cAMP) response elements that bind CREB, a trophoblast-specific element that binds TSEB, and a sequence motif, AGATAA, that matches the consensus binding site for a family of transcription factors termed the GATA-binding proteins. In pituitary gonadotropes, the cAMP response elements remain important for expression, TSEB is absent, and elements further upstream participate in tissue-specific expression. Here we establish a regulatory role for the GATA element in both the placenta and pituitary by demonstrating that a mutation of this element decreases alpha-subunit gene expression 15-fold in JEG-3 human placental cells and 2.5-fold in alpha T3-1 mouse pituitary gonadotropes. In JEG-3 cells, human GATA-2 (hGATA-2) and hGATA-3 are highly expressed and both proteins bind to the alpha-subunit gene GATA element. In alpha T3-1 cells, the GATA motif is bound by mouse GATA-2 (mGATA-2) and an mGATA-4-related protein. Cotransfection of hGATA-2 or hGATA-3 into alpha T3-1 cells activates the alpha-subunit gene threefold. These studies establish a role for the GATA-binding proteins in placental and pituitary alpha-subunit gene expression, significantly expanding the known target genes of GATA-2, GATA-3, and perhaps GATA-4.

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