scholarly journals Identifying Transcription Regulatory Elements in the Human and Mouse Genomes Using Tissue-specific Gene Expression Profiles

2007 ◽  
Vol 4 (2) ◽  
pp. 1-23
Author(s):  
Amitava Karmaker ◽  
Kihoon Yoon ◽  
Mark Doderer ◽  
Russell Kruzelock ◽  
Stephen Kwek
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Tissue Specific Gene ◽  
Human And Mouse

Summary Revealing the complex interaction between trans- and cis-regulatory elements and identifying these potential binding sites are fundamental problems in understanding gene expression. The progresses in ChIP-chip technology facilitate identifying DNA sequences that are recognized by a specific transcription factor. However, protein-DNA binding is a necessary, but not sufficient, condition for transcription regulation. We need to demonstrate that their gene expression levels are correlated to further confirm regulatory relationship. Here, instead of using a linear correlation coefficient, we used a non-linear function that seems to better capture possible regulatory relationships. By analyzing tissue-specific gene expression profiles of human and mouse, we delineate a list of pairs of transcription factor and gene with highly correlated expression levels, which may have regulatory relationships. Using two closely-related species (human and mouse), we perform comparative genome analysis to cross-validate the quality of our prediction. Our findings are confirmed by matching publicly available TFBS databases (like TRANFAC and ConSite) and by reviewing biological literature. For example, according to our analysis, 80% and 85.71% of the targets genes associated with E2F5 and RELB transcription factors have the corresponding known binding sites. We also substantiated our results on some oncogenes with the biomedical literature. Moreover, we performed further analysis on them and found that BCR and DEK may be regulated by some common transcription factors. Similar results for BTG1, FCGR2B and LCK genes were also reported.

scholarly journals Self-reporting transposons enable simultaneous readout of gene expression and transcription factor binding in single cells

2019 ◽  
Author(s):  
Arnav Moudgil ◽  
Michael N. Wilkinson ◽  
Xuhua Chen ◽  
June He ◽  
Alex J. Cammack ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Single Cell ◽  
Binding Sites ◽  
Expression Profiles ◽  
Single Cells ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Specific Cell

AbstractIn situ measurements of transcription factor (TF) binding are confounded by cellular heterogeneity and represent averaged profiles in complex tissues. Single cell RNA-seq (scRNA-seq) is capable of resolving different cell types based on gene expression profiles, but no technology exists to directly link specific cell types to the binding pattern of TFs in those cell types. Here, we present self-reporting transposons (SRTs) and their use in single cell calling cards (scCC), a novel assay for simultaneously capturing gene expression profiles and mapping TF binding sites in single cells. First, we show how the genomic locations of SRTs can be recovered from mRNA. Next, we demonstrate that SRTs deposited by the piggyBac transposase can be used to map the genome-wide localization of the TFs SP1, through a direct fusion of the two proteins, and BRD4, through its native affinity for piggyBac. We then present the scCC method, which maps SRTs from scRNA-seq libraries, thus enabling concomitant identification of cell types and TF binding sites in those same cells. As a proof-of-concept, we show recovery of cell type-specific BRD4 and SP1 binding sites from cultured cells. Finally, we map Brd4 binding sites in the mouse cortex at single cell resolution, thus establishing a new technique for studying TF biology in situ.

scholarly journals GeneTIER: prioritization of candidate disease genes using tissue-specific gene expression profiles

2015 ◽  
Vol 31 (16) ◽  
pp. 2728-2735 ◽  
Author(s):  
Agne Antanaviciute ◽  
Catherine Daly ◽  
Laura A. Crinnion ◽  
Alexander F. Markham ◽  
Christopher M. Watson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Specific Gene ◽  
Disease Genes ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Specific Gene Expression

scholarly journals Mechanisms of YAP/TAZ transcriptional control

Cell Stress ◽  
2021 ◽  
Vol 5 (11) ◽  
pp. 167-172
Author(s):  
Giusy Battilana ◽  
Francesca Zanconato ◽  
Stefano Piccolo
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Cell Transformation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Chromatin Regulators ◽  
Small Set

Dysregulated gene expression is intrinsic to cell transformation, tumorigenesis and metastasis. Cancer-specific gene-expression profiles stem from gene regulatory networks fueled by genetic and epigenetic defects, and by abnormal signals of the tumor microenvironment. These oncogenic signals ultimately engage the transcriptional machinery on the cis -regulatory elements of a host of effector genes, through recruitment of transcription factors (TFs), co-activators and chromatin regulators. That said, whether gene -expression in cancer cells is the chaotic product of myriad regulations or rather a relatively ordered process orchestrated by few TFs (master regulators) has long remained enigmatic. Recent work on the YAP/TAZ co-activators has been instrumental to break new ground into this outstanding issue, revealing that tumor cells hijack growth programs that are active during development and regeneration through engagement of a small set of interconnected TFs and their nuclear partners.

scholarly journals Transcrptome analysis via photo-isolation chemistry

2021 ◽  
Author(s):  
Mizuki Honda ◽  
Shinya Oki ◽  
Ryuichi Kimura ◽  
Akihito Harada ◽  
Kazumitsu Maehara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uv Irradiation ◽  
Tissue Section ◽  
Reverse Transcription ◽  
Spatial Information ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Specific Gene ◽  
Tissue Specific Gene ◽  
Tissue Sections

Abstract To gain insights into tissue-specific gene expression in multicellular systems, gene expression profiles are required to be precisely linked with spatial information. Here, we establish a hight-depth spatial transcriptomics method, photo-isolation chemistrty (PIC), which is able to isolate gene expression profiles only from UV-irradiatied region out of whole tissue section. This method performs reverse transcription on tissue sections using photocaged oligo DNAs. After the UV irradiation, the cDNAs in the irradiated regions are allowed to be amplified and sequenced, thereby providing gene expression profiles linked with spatial information.

scholarly journals The Th1 cell regulatory circuitry is largely conserved between human and mouse

2021 ◽  
Vol 4 (11) ◽  
pp. e202101075
Author(s):  
Stephen Henderson ◽  
Venu Pullabhatla ◽  
Arnulf Hertweck ◽  
Emanuele de Rinaldis ◽  
Javier Herrero ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Infectious Diseases ◽  
Binding Sites ◽  
Target Genes ◽  
Specific Gene ◽  
Type I ◽  
A Genome ◽  
Species Specific

Gene expression programs controlled by lineage-determining transcription factors are often conserved between species. However, infectious diseases have exerted profound evolutionary pressure, and therefore the genes regulated by immune-specific transcription factors might be expected to exhibit greater divergence. T-bet (Tbx21) is the immune-specific, lineage-specifying transcription factor for T helper type I (Th1) immunity, which is fundamental for the immune response to intracellular pathogens but also underlies inflammatory diseases. We compared T-bet genomic targets between mouse and human CD4+ T cells and correlated T-bet binding patterns with species-specific gene expression. Remarkably, we found that the majority of T-bet target genes are conserved between mouse and human, either via preservation of binding sites or via alternative binding sites associated with transposon-linked insertion. Species-specific T-bet binding was associated with differences in transcription factor–binding motifs and species-specific expression of associated genes. These results provide a genome-wide cross-species comparison of Th1 gene regulation that will enable more accurate translation of genetic targets and therapeutics from pre-clinical models of inflammatory and infectious diseases and cancer into human clinical trials.

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