scholarly journals Across-tissue expression and evolution of genes controlled by the Aire transcription factor

Genomics ◽  
2006 ◽  
Vol 88 (4) ◽  
pp. 462-467 ◽  
Author(s):  
Austin L. Hughes ◽  
Robert Friedman
Keyword(s):  
Transcription Factor ◽  
Tissue Expression

scholarly journals Understanding Tissue-specific Gene Regulation

2017 ◽  
Author(s):  
Abhijeet R. Sonawane ◽  
John Platig ◽  
Maud Fagny ◽  
Cho-Yi Chen ◽  
Joseph N. Paulson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Control ◽  
Tissue Specificity ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
Gene Set Enrichment Analysis ◽  
Specific Gene ◽  
Tissue Specific ◽  
Network Nodes ◽  
Transcription Factor Expression

Although all human tissues carry out common processes, tissues are distinguished by gene expres-sion patterns, implying that distinct regulatory programs control tissue-specificity. In this study, we investigate gene expression and regulation across 38 tissues profiled in the Genotype-Tissue Expression project. We find that network edges (transcription factor to target gene connections) have higher tissue-specificity than network nodes (genes) and that regulating nodes (transcription factors) are less likely to be expressed in a tissue-specific manner as compared to their targets (genes). Gene set enrichment analysis of network targeting also indicates that regulation of tissue-specific function is largely independent of transcription factor expression. In addition, tissue-specific genes are not highly targeted in their corresponding tissue-network. However, they do assume bottleneck positions due to variability in transcription factor targeting and the influence of non-canonical regulatory interactions. These results suggest that tissue-specificity is driven by context-dependent regulatory paths, providing transcriptional control of tissue-specific processes.

scholarly journals The HD-ZIP IV transcription factor Tril regulates fruit spine density through gene dosage effects in cucumber

2020 ◽  
Vol 71 (20) ◽  
pp. 6297-6310
Author(s):  
Hui Du ◽  
Gang Wang ◽  
Jian Pan ◽  
Yue Chen ◽  
Tingting Xiao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Genetic Interaction ◽  
Gene Dosage ◽  
Expression Patterns ◽  
Tissue Expression ◽  
Spine Density ◽  
Gene Dosage Effect ◽  
Gene Dosage Effects ◽  
Transgenic Lines ◽  
Mutant Phenotypes

Abstract Trichomes and fruit spines are important traits that directly affect the appearance quality and commercial value of cucumber (Cucumis sativus). Tril (Trichome-less), encodes a HD-Zip IV transcription factor that plays a crucial role in the initiation of trichomes and fruit spines, but little is known about the details of the regulatory mechanisms involved. In this study, analysis of tissue expression patterns indicated that Tril is expressed and functions in the early stages of organ initiation and development. Expression of Tril under the control of its own promoter (the TrilPro::Tril-3*flag fragment) could partly rescue the mutant phenotypes of tril, csgl3 (cucumber glabrous 3, an allelic mutant of tril), and fs1 (few spines 1, a fragment substitution in the Tril promoter region), providing further evidence that Tril is responsible for the initiation of trichomes and fruit spines. In lines with dense spine, fs1-type lines, and transgenic lines of different backgrounds containing the TrilPro::Tril-3*flag foreign fragment, spine density increased in conjunction with increases in Tril expression, indicating that Tril has a gene dosage effect on fruit spine density in cucumber. Numerous Spines (NS) is a negative regulatory factor of fruit spine density. Characterization of the molecular and genetic interaction between Tril and NS/ns demonstrated that Tril functions upstream of NS with respect to spine initiation. Overall, our results reveal a novel regulatory mechanism governing the effect of Tril on fruit spine development, and provide a reference for future work on breeding for physical quality in cucumber.

Chromosomal location and tissue expression of the gene encoding the adenovirus E1A-regulated transcription factor E4F in humans and mice

1998 ◽  
Vol 9 (4) ◽  
pp. 320-323 ◽  
Author(s):  
Robert J. Rooney ◽  
Rachael R. Daniels ◽  
Nancy A. Jenkins ◽  
Debra J. Gilbert ◽  
Kristen Rothammer ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Chromosomal Location ◽  
Tissue Expression ◽  
Gene Encoding ◽  
Adenovirus E1a

Zinc finger transcription factor Egr-1 is involved in stimulation of NHE2 gene expression by phorbol 12-myristate 13-acetate

2005 ◽  
Vol 289 (4) ◽  
pp. G653-G663 ◽  
Author(s):  
Jaleh Malakooti ◽  
Ricardo Sandoval ◽  
Vanchad C. Memark ◽  
Pradeep K. Dudeja ◽  
Krishnamurthy Ramaswamy
Keyword(s):  
Transcription Factor ◽  
Tissue Expression ◽  
Pcr Analysis ◽  
Transcriptional Level ◽  
Cis Acting ◽  
Nuclear Extracts ◽  
Regulated Expression ◽  
Dna Fragment ◽  
Molecular Signals ◽  
Basal Transcriptional Activity

The apical membrane Na+/H+exchanger isoforms NHE2 and NHE3 are involved in transepithelial Na+absorption in the intestine. However, they exhibit differences in their pattern of tissue expression and regulation of their activity by various molecular signals. To study the mechanisms involved in the transcriptional regulation of these genes, we characterized cis-acting elements within the human NHE2 promoter that regulate NHE2 promoter expression in C2BBe1 cells. A small DNA region (−85/+249) was involved in the regulation of basal transcriptional activity of the NHE2 promoter as determined by transient transfection assays. RT-PCR analysis showed that NHE2 mRNA was upregulated in response to phorbol 12-myristate 13-acetate (PMA). Results from actinomycin D-treated cells indicated that the regulation of the NHE2 gene by PMA occurs in part at the transcriptional level. Furthermore, PMA treatment led to a 100% increase in promoter activity through elements located on the −415/+249 DNA fragment. A PMA-induced nuclear factor that bound to the NHE2 promoter was identified as the transcription factor Egr-1. We identified two PMA response elements in the −415/+1 promoter region that bind to Sp1 and Sp3 in untreated nuclear extracts and to Egr-1 in PMA-treated nuclear extracts. In cotransfection experiments, Egr-1 was able to transactivate the NHE2 promoter. Our data indicate that Egr-1 may play a key role in regulated expression of the human NHE2 gene.

scholarly journals Digital analysis of hormonal immunostaining in pituitary adenomas classified according to WHO 2017 criteria and correlation with preoperative laboratory findings

2020 ◽  
Vol 48 (6) ◽  
pp. E12
Author(s):  
João Vitor Gerdulli Tamanini ◽  
Mateus Dal Fabbro ◽  
Leandro Luiz Lopes de Freitas ◽  
José Vassallo ◽  
Luciano de Souza Queiroz ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Serum Insulin ◽  
Laboratory Data ◽  
Pituitary Tumors ◽  
Tissue Expression ◽  
Primary Antibody ◽  
Cushing Disease ◽  
Laboratory Findings ◽  
Serum Gh ◽  
Serum Acth

OBJECTIVEThe authors sought to evaluate clinical and laboratory data from pituitary adenoma (PA) patients with functioning PA (associated with acromegaly [n = 10] or Cushing disease [n = 10]) or nonfunctioning PA (NFPA; n = 10) that were classified according to 2017 WHO criteria (based on the expression of the transcription factors pituitary-specific positive transcription factor 1 [Pit-1], a transcription factor member of the T-box family [Tpit], and steroidogenic factor 1 [SF-1]) and to assess the immunostaining results for growth hormone (GH) and adrenocorticotropic hormone (ACTH) in the corresponding tumors.METHODSClinical and laboratory data were collected retrospectively. The percentage of tumoral cells positive for Pit-1, Tpit, or SF-1 was assessed and ImageJ software was used to evaluate immunopositivity in PAs with 2 different antibodies against GH (primary antibody 1 [AbGH-1] and primary antibody 2 [AbGH-2]) and 2 different antibodies against ACTH (primary antibody 1 [AbACTH-1] and primary antibody 2 [AbACTH-2]).RESULTSCells with positive Pit-1 staining were more frequently observed in lesions from patients with acromegaly (acromegaly group) than in lesions from patients with Cushing disease (Cushing group; p < 0.001) and those from patients with NFPA (NFPA group; p < 0.001). The percentage of Tpit-positive cells was higher in the Cushing group than in the acromegaly (p < 0.001) and NFPA (p < 0.001) groups. No difference was detected regarding SF-1 frequency among all groups (p = 0.855). In acromegalic individuals, GH immunostaining levels varied depending on the antibody employed, and only one of the antibodies (AbGH-2) yielded higher values in comparison with the values for NFPA patients (p < 0.001). For all of the antibodies employed, no significant correlations were detected between GH tissue expression and the laboratory data (serum GH vs AbGH-1, p = 0.933; serum GH vs AbGH-2, p = 0.853; serum insulin-like growth factor–1 [IGF-1] vs AbGH-1, p = 0.407; serum IGF-1 vs AbGH-2, p = 0.881). In the Cushing group data, both antibodies showed similar ACTH tissue expression, which was higher than that obtained in the NFPA group (p < 0.001). There were no significant associations between ACTH immunohistochemical findings and ACTH serum levels (serum ACTH vs AbACTH-1, p = 0.651; serum ACTH vs AbACTH-2, p = 0.987). However, ACTH immunostaining evaluated with AbACTH-1 showed a significant correlation with 24-hour urinary cortisol (24-hour cortisol vs AbACTH-1, p = 0.047; 24-hour cortisol vs AbACTH-2, p = 0.071).CONCLUSIONSImmunostaining for Pit-1 and Tpit accurately identified lesions associated with acromegaly and Cushing disease, respectively. Conversely, SF-1 did not differentiate NFPA from lesions of the other two groups. Regarding hormonal tissue detection, results of the current investigation indicate that different antibodies may lead not only to divergent immunohistochemical results but also to lack of correlation with laboratory findings. Finally, PA classification based on transcription factor expression (Pit-1, Tpit, and SF-1), as proposed by the 2017 WHO classification of pituitary tumors, may avoid the limitations of PA classification based solely on digital immunohistochemical detection of hormones.

scholarly journals Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk

2017 ◽  
Author(s):  
Yakir A Reshef ◽  
Hilary K Finucane ◽  
David R Kelley ◽  
Alexander Gusev ◽  
Dylan Kotliar ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Complex Traits ◽  
Biological Process ◽  
Disease Risk ◽  
Tissue Expression ◽  
Regulatory Elements ◽  
Disease Genes ◽  
Disease Etiology ◽  
Causal Genes ◽  
Trait Associations

AbstractBiological interpretation of GWAS data frequently involves analyzing unsigned genomic annotations comprising SNPs involved in a biological process and assessing enrichment for disease signal. However, it is often possible to generate signed annotations quantifying whether each SNP allele promotes or hinders a biological process, e.g., binding of a transcription factor (TF). Directional effects of such annotations on disease risk enable stronger statements about causal mechanisms of disease than enrichments of corresponding unsigned annotations. Here we introduce a new method, signed LD profile regression, for detecting such directional effects using GWAS summary statistics, and we apply the method using 382 signed annotations reflecting predicted TF binding. We show via theory and simulations that our method is well-powered and is well-calibrated even when TF binding sites co-localize with other enriched regulatory elements, which can confound unsigned enrichment methods. We further validate our method by showing that it recovers known transcriptional regulators when applied to molecular QTL in blood. We then apply our method to eQTL in 48 GTEx tissues, identifying 651 distinct TF-tissue expression associations at per-tissue FDR < 5%, including 30 associations with robust evidence of tissue specificity. Finally, we apply our method to 46 diseases and complex traits (averageN= 289,617) and identify 77 annotation-trait associations at per-trait FDR < 5% representing 12 independent TF-trait associations, and we conduct gene-set enrichment analyses to characterize the underlying transcriptional programs. Our results implicate new causal disease genes (including causal genes at known GWAS loci), and in some cases suggest a detailed mechanism for a causal gene’s effect on disease. Our method provides a new way to leverage functional data to draw inferences about disease etiology.

Transcription factor/DNA interactions visualized by electron spectroscopic imaging

1992 ◽  
Vol 50 (1) ◽  
pp. 450-451
Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Phosphorus Content ◽  
Spectroscopic Imaging ◽  
Electron Spectroscopic Imaging ◽  
Dna Backbone ◽  
Two Parameters ◽  
High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

The role of transcription factor Egr‐1 in IL‐1 up‐regulation of tubular CD44 expression

Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A92-A92
Author(s):  
Takazoe K ◽  
Foti R ◽  
Hurst La ◽  
Atkins Rc ◽  
Nikolic‐Paterson DJ.
Keyword(s):  
Transcription Factor ◽  
Cd44 Expression
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