Promoter analysis and transcription profiling: Integration of genetic data enhances understanding of gene expression

2004 ◽  
Vol 120 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Mauritz Venter ◽  
Frederik C. Botha
Genomics ◽  
1999 ◽  
Vol 62 (2) ◽  
pp. 260-271 ◽  
Author(s):  
Stéphane Schurmans ◽  
Roberto Carrió ◽  
Jens Behrends ◽  
Valérie Pouillon ◽  
Jesús Merino ◽  
...  

2006 ◽  
Vol 85 (6) ◽  
pp. 505-509 ◽  
Author(s):  
R.B. Rutherford ◽  
B.L. Foster ◽  
T. Bammler ◽  
R.P. Beyer ◽  
S. Sato ◽  
...  

Genetic data from humans and mice reveal that the formation of cementum is sensitive to intra- and extracellular phosphate/pyrophosphate distribution. The intracellular molecular pathways whereby altered levels of extracellular phosphate concentration may affect cementum formation have not been elucidated. To initiate inquiry, we have studied the temporal effects of extracellular phosphate on global patterns of gene expression in a line of immortalized mouse cementoblasts. Total RNA from cultured cementoblasts treated with 5 mM inorganic phosphate over a designated time period, from 1–48 hrs, was analyzed for global patterns of gene expression by means of DNA microarrays representing the complete mouse genome. Analyses of significant hybridization signals indicated that 5 mM extracellular phosphate alters the expression of genes comprising several gene ontology (GO) groups, including transcription factor activity and Wnt signaling.


2003 ◽  
Vol 10 (1) ◽  
pp. 98-110 ◽  
Author(s):  
Hsin-hsin Kao ◽  
Ming-shi Chang ◽  
Jan-fang Cheng ◽  
Jin-ding Huang

2003 ◽  
Vol 328 (5) ◽  
pp. 1197
Author(s):  
Ping Qiu ◽  
Ling Qin ◽  
Richard P. Sorrentino ◽  
Jonathan R. Greene ◽  
Nicola C. Partridge ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2821-2821
Author(s):  
Hisayuki Yokoyama ◽  
Hideo Harigae ◽  
Shinichiro Takahashi ◽  
Yoko Okitsu ◽  
Johji Yamamoto ◽  
...  

Abstract Aplastic anemia (AA) is characterized by reduced hematopoiesis resulting in pancytopenia. It is suggested that a certain immunological attack to hematopoietic stem cells play an important role in developing AA. However, limited information is available for the intrinsic characteristics of stem cells in AA. Previous work in our laboratory showed decreased expression of GATA-2 gene in CD34 positive cells in AA, suggesting that there is an aberrant expression of stem cell-specific genes in stem cells in AA. Recently it is emerged that some genes such as HOXB4 and BMI-1, function for the proliferation and maintenance of stem cells. In this study, we examined expression levels of HOXB4 and BMI-1 in CD34 positive cells by quantitative PCR in 10 patients with AA and 13 with idiopathic thrombocytopenic purpura (ITP). Between these two factors, the expression level of HOXB4 was markedly decreased in AA compared with in ITP, whereas that of BMI-1 was not. Moreover, the expression level of GATA-2 in these populations was significantly correlated to HOXB4 gene expression (Spearman’s rank correlation, r=0.6573 p<0.01) compared to that of BMI-1(r=0.4107, p>0.05). As they functions as a transcription factor, these results raise the possibility that GATA-2 and HOXB4 regulate each other. To explore this possibility, first, we cloned HOXB4 5′flanking region by PCR and performed promoter analysis. Since the previous report showed that the region from −164 to −116 was important for promoter activity of HOXB4 gene, we focused on a GATA element located at −160. When this element was deleted, the reporter activity was decreased to 60% of wild-type in K562 cells. Furthermore, co-transfection of GATA-2 expression vector significantly activates the reporter gene in a dose dependent manner. EMSA revealed that GATA-2 binds specifically to this element. On the other hand, the active region both of exon 1S and 1G promoter of GATA-2 gene, which was identified by the promoter analysis, did not contain the consensus sequence recognized by HOXB4. These findings suggest that in stem cells in AA, the decreased expression of GATA-2 gene lead to the reduced HOXB4 gene expression, which may responsible for the development of the disease.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yunyun Dong ◽  
Wenkai Yang ◽  
Jiawen Wang ◽  
Juanjuan Zhao ◽  
Yan Qiang ◽  
...  

Abstract Background Lung cancer is one of the most common types of cancer, among which lung adenocarcinoma accounts for the largest proportion. Currently, accurate staging is a prerequisite for effective diagnosis and treatment of lung adenocarcinoma. Previous research has used mainly single-modal data, such as gene expression data, for classification and prediction. Integrating multi-modal genetic data (gene expression RNA-seq, methylation data and copy number variation) from the same patient provides the possibility of using multi-modal genetic data for cancer prediction. A new machine learning method called gcForest has recently been proposed. This method has been proven to be suitable for classification in some fields. However, the model may face challenges when applied to small samples and high-dimensional genetic data. Results In this paper, we propose a multi-weighted gcForest algorithm (MLW-gcForest) to construct a lung adenocarcinoma staging model using multi-modal genetic data. The new algorithm is based on the standard gcForest algorithm. First, different weights are assigned to different random forests according to the classification performance of these forests in the standard gcForest model. Second, because the feature vectors generated under different scanning granularities have a diverse influence on the final classification result, the feature vectors are given weights according to the proposed sorting optimization algorithm. Then, we train three MLW-gcForest models based on three single-modal datasets (gene expression RNA-seq, methylation data, and copy number variation) and then perform decision fusion to stage lung adenocarcinoma. Experimental results suggest that the MLW-gcForest model is superior to the standard gcForest model in constructing a staging model of lung adenocarcinoma and is better than the traditional classification methods. The accuracy, precision, recall, and AUC reached 0.908, 0.896, 0.882, and 0.96, respectively. Conclusions The MLW-gcForest model has great potential in lung adenocarcinoma staging, which is helpful for the diagnosis and personalized treatment of lung adenocarcinoma. The results suggest that the MLW-gcForest algorithm is effective on multi-modal genetic data, which consist of small samples and are high dimensional.


2004 ◽  
Vol 15 (10) ◽  
pp. 4490-4499 ◽  
Author(s):  
Doreen Harcus ◽  
André Nantel ◽  
Anne Marcil ◽  
Tracey Rigby ◽  
Malcolm Whiteway

We used transcription profiling in Candida albicans to investigate cellular regulation involving cAMP. We found that many genes require the adenylyl cyclase Cdc35p for proper expression. These include genes encoding ribosomal subunit proteins and RNA polymerase subunit proteins, suggesting that growth could be controlled in part by cAMP-mediated modulation of gene expression. Other genes influenced by loss of adenylyl cyclase are involved in metabolism, the cell wall, and stress response and include a group of genes of unknown function that are unique to C. albicans. The profiles generated by loss of the adenylyl cyclase regulator Ras1p and a downstream effector Efg1p were also examined. The loss of Ras1p function disturbs the expression of a subset of the genes regulated by adenylyl cyclase, suggesting both that the primary role of Ras1p in transcriptional regulation involves its influence on the function of Cdc35p and that there are Ras1p independent roles for Cdc35p. The transcription factor Efg1p is also needed for the expression of many genes; however, these genes are distinct from those modulated by Cdc35p with the exception of a class of hyphal-specific genes. Therefore transcription profiling establishes that cAMP plays a key role in the overall regulation of gene expression in C. albicans, and enhances our detailed understanding of the circuitry controlling this regulation.


2002 ◽  
Vol 184 (16) ◽  
pp. 4612-4616 ◽  
Author(s):  
Alex S. Beliaev ◽  
Dorothea K. Thompson ◽  
Matthew W. Fields ◽  
Liyou Wu ◽  
Douglas P. Lies ◽  
...  

ABSTRACT DNA microarrays were used to examine the effect of an insertional mutation in the Shewanella oneidensis etrA (electron transport regulator) locus on gene expression under anaerobic conditions. The mRNA levels of 69 genes with documented functions in energy and carbon metabolism, regulation, transport, and other cellular processes displayed significant alterations in transcript abundance in an etrA-mutant genetic background. This is the first microarray study indicating a possible involvement of EtrA in the regulation of gene expression in S. oneidensis MR-1.


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