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A Quantitative Model of Transcriptional Regulation Reveals the Influence of Binding Location on Expression

Kenzie D. MacIsaac, Kinyui A. Lo, William Gordon, Shmulik Motola, Tali Mazor, Ernest Fraenkel, Yitzhak Pilpel
2010 PLoS Computational Biology  
We present a quantitative model of transcriptional regulation that suggests the contribution of each binding site to tissue-specific gene expression depends strongly on its position relative to the transcription  ...  Our model suggests that, for the transcription factors profiled in these cell types, a regulatory site's influence on expression falls off almost linearly with distance from the transcription start site  ...  To further understand the relationship between expression and regulator binding location we developed a simple quantitative model that predicts transcription level as a function of transcription factor  ... 
doi:10.1371/journal.pcbi.1000773 pmid:20442865 pmcid:PMC2861697 fatcat:yrvecivdkzhsfomo24pwqwwzsq

P188 REDUCED METALLOTHIONEIN EXPRESSION IN COLONIC CROHN'S DISEASE: EVIDENCE FOR A NEW DISEASE-MODIFYING GENE

D. Laukens, H. Peeters, A. Waeytens, S. Bogaert, B. Van der Cryssen, D. Elewaut, F. DeKeyser, H. Mielants, C. Cuvelier, K. Knecht, P. Van Hummelen, J. Del-Favero (+3 others)
2008 Journal of Crohn?s and Coltis Supplements  
The gene for MRE-binding transcription factor 1 (MTF1) was screened for mutations in 96 CD patients and the influence of a polymorphism on transcriptional activity was assessed in a luciferase reporter  ...  Sequence analysis of the main transcriptional regulator of MTs, MTF1, revealed two coding mutations: Asp63Glu in 5 patients and Glu385Lys in 2 patients.  ...  The gene for MRE-binding transcription factor 1 (MTF1) was screened for mutations in 96 CD patients and the influence of a polymorphism on transcriptional activity was assessed in a luciferase reporter  ... 
doi:10.1016/s1873-9954(08)70199-x fatcat:iwtpmnx4brhdtjssmyp5nfazdm

Transcriptional precision and accuracy in development: from measurements to models and mechanisms

Lital Bentovim, Timothy T. Harden, Angela H. DePace
2017 Development  
modeling to exploit the wealth of quantitative data and advance our understanding of animal transcription.  ...  We also highlight selected examples in which the coupling of mathematical modeling with experimental approaches has provided important mechanistic insights, and call for a more expansive use of mathematical  ...  Acknowledgements We thank Mounia Lagha, Ian Swinburne, Tom Hiscock, our reviewers and all members of the A.H.D. lab for helpful comments and feedback on the manuscript; and Heng Xu, Ido Golding, Shawn  ... 
doi:10.1242/dev.146563 pmid:29089359 fatcat:rdt7winbj5ewvghv2b7fe2bhoe

Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity

Jeehae Park, Javier Estrada, Gemma Johnson, Ben J Vincent, Chiara Ricci-Tam, Meghan DJ Bragdon, Yekaterina Shulgina, Anna Cha, Zeba Wunderlich, Jeremy Gunawardena, Angela H DePace
2019 eLife  
We systematically interrogate cis and trans factors that influence the shape and position of expression driven by HbP2, and find that the prevailing model, based on pairwise cooperative binding of Bcd  ...  Here we examine the hunchback P2 (HbP2) enhancer which drives a sharp expression pattern in the Drosophila blastoderm embryo in response to the transcriptional activator Bicoid (Bcd).  ...  Acknowledgements The authors wish to acknowledge all members of the DePace and Gunawardena groups, for their helpful feedback on the work and manuscript.  ... 
doi:10.7554/elife.41266 pmid:31223115 pmcid:PMC6588347 fatcat:yxv7u4pavjaepibzt67e6kzi3u

Genomic Determinants of Vitamin D-Regulated Gene Expression [chapter]

J. Wesley Pike, Mark B. Meyer, Nancy A. Benkusky, Seong Min Lee, Hillary St. John, Alex Carlson, Melda Onal, Sohel Shamsuzzaman
2016 Vitamines and Hormones  
Insight into mechanisms that link the actions of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) to the regulation of gene expression has evolved extensively since the initial discovery of a nuclear protein  ...  These studies highlight the role of chromatin in the expression of genes and the dynamic impact of the epigenetic landscape that contextualizes individual gene loci thus influencing the VDR's transcriptional  ...  Acknowledgments We acknowledge the helpful contributions of members of the Pike laboratory to this review and financial support from National Institutes of Health grants from NIDDK (DK-072281, DK-074993  ... 
doi:10.1016/bs.vh.2015.10.011 pmid:26827947 pmcid:PMC5113140 fatcat:au3qm2ci5begtg3eacblvg7e3u

Expression Levels of LCORL Are Associated with Body Size in Horses

Julia Metzger, Rahel Schrimpf, Ute Philipp, Ottmar Distl, Elissa Z. Cameron
2013 PLoS ONE  
Genome-wide association analyses revealed the highest associated quantitative trait locus for height at the withers on horse chromosome (ECA) 3 upstream of the candidate gene LCORL.  ...  Bioinformatic analyses indicated that this SNP T.C mutation is disrupting a putative binding site of the transcription factor TFIID which is important for the transcription process of genes involved in  ...  Acknowledgments We thank the Hanoverian Studbook Society for providing data and samples of Hanoverian warmblood horses.  ... 
doi:10.1371/journal.pone.0056497 pmid:23418579 pmcid:PMC3572084 fatcat:6ehtxe6c5ndx3hmdp7evbezkzq

Population-scale genetic control of alternative polyadenylation and its association with human diseases

2021 Quantitative Biology  
Alternative polyadenylation (APA) plays an essential role in post-transcriptional regulation for most human genes.  ...  By employing different poly(A) sites, genes can either shorten or extend the 3′-UTRs that contain cis-regulatory elements such as miRNAs or RNAbinding protein binding sites.  ...  The Wagner lab acknowledges support from the National Institutes of Health grant R01-GM134539 (E.J.W).  ... 
doi:10.15302/j-qb-021-0252 fatcat:pmdobqie7fdijbk4odcz3tcbvy

Single-Molecule Insights on the Human RNA Polymerase II Transcription Regulation: Assembly of the Pre-Initiation Complex, Re-Initiation Scaffold, and the Roles of Activators

Zhengjian Zhang, Andrey Revyakin, Yu-Chih Tsai, Robert Coleman, Yan Li, Jonas Kolach, Steve Chu, Robert Tjian
2012 Biophysical Journal  
Based on our results, we present a rate-equation based model to highlight potential mechanisms of promoter interaction.  ...  In heterologous gene expression, a module with two gene circuits responsible for expression of a foreign gene of interest and selection is integrated into the host cell genome.  ...  Experimental and Stochastic Model Analysis of the Influence of SIC1, CLN2 and CLB5 Transcriptional Noise on the Timing Regulation of G1/S Transition in S.  ... 
doi:10.1016/j.bpj.2011.11.1255 fatcat:56lmgc242nfqrehhe5whzrct7q

From association to mechanism in complex disease genetics: the role of the 3D genome

Yao Fu, Kandice L Tessneer, Chuang Li, Patrick M Gaffney
2018 Arthritis Research & Therapy  
We then highlight examples from the literature that illustrate how functional mapping of the 3D genome can assist in defining mechanisms that influence pathogenic gene expression.  ...  Enhancers function within the context of the three-dimensional (3D) genome to form long-range DNA looping events with target gene promoters that spatially and temporally regulate gene expression.  ...  Enhancers influence gene expression by delivering their payload of transcription factors to the gene promoter most often located on the same chromosome, but at varying distances, through a process of DNA  ... 
doi:10.1186/s13075-018-1721-x fatcat:hfqqfrdm2fcyffaxmjvninitlq

Minireview: Applications of Next-Generation Sequencing on Studies of Nuclear Receptor Regulation and Function

Clifford A. Meyer, Qianzi Tang, X. Shirley Liu
2012 Molecular Endocrinology  
Next-generation sequencing technologies have expanded the experimental possibilities for studying the genome-wide regulation of transcription by nuclear receptors, their collaborating transcription factors  ...  Beato M, Vicent GP 2012 Impact of chromatin structure and dynamics on PR signaling. The initial steps in hormonal gene regulation. Mol Cell Endocrinol 357:37-42 34.  ...  In our model, the regulatory potential of each TF-binding site is a decreasing function of the genomic distance between the site and the TSS, and the regulatory effect on the TSS is a sum of the influence  ... 
doi:10.1210/me.2012-1150 pmid:22930692 pmcid:PMC3458226 fatcat:iwrpsses6zduvolnttkefszrge

Exploring the function of genetic variants in the non-coding genomic regions: approaches for identifying human regulatory variants affecting gene expression

M. J. Li, B. Yan, P. C. Sham, J. Wang
2014 Briefings in Bioinformatics  
In this review, we will focus on current approaches to identify functional RVs affecting transcriptional gene regulation.  ...  Taken together, all these findings shed light on importance of function investigation of RVs in affecting gene regulation.  ...  We outlined the biological mechanisms of RVs influencing transcriptional gene regulation in Table 1 .  ... 
doi:10.1093/bib/bbu018 pmid:24916300 fatcat:wpya77tqkrcxlo7s32s7rr33ie

Modeling transcriptional networks regulating secondary growth and wood formation in forest trees

Lijun Liu, Vladimir Filkov, Andrew Groover
2013 Physiologia Plantarum : An International Journal for Plant Biology  
A large number of genes have been identified that are expressed during the radial woody growth of tree stems (secondary growth), but a comprehensive understanding of how these genes interact to influence  ...  Modeling transcriptional networks has recently been made tractable by next-generation sequencingbased technologies that can comprehensively catalog gene expression and transcription factor-binding genome-wide  ...  One way to build a predictive model of gene expression is in terms of the binding events modeled as either overrepresented motifs or ChIP-seq binding events in gene's cis-regions (Bussemaker et al. 2001  ... 
doi:10.1111/ppl.12113 pmid:24117954 fatcat:7uyqmwldnrcsvofbvm5c5tb43u

Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta

Isabel Iglesias-Platas, Alex Martin-Trujillo, Paolo Petazzi, Amy Guillaumet-Adkins, Manel Esteller, David Monk
2014 Human Molecular Genetics  
In addition, PLAGL1 binding and expression also correlate with expression levels of metabolic regulator genes SLC2A4, TCF4 and PPARg1.  ...  Genomic imprinting is the epigenetic process that results in monoallelic expression of genes depending on parental origin.  ...  to the collection of samples.  ... 
doi:10.1093/hmg/ddu347 pmid:24993786 pmcid:PMC4334785 fatcat:bmawcs77kfhahgzv55j7jgvdmu

A Bacterial Pathogen Flips the Riboswitch

Bobbi Xayarath, Nancy E. Freitag
2009 Cell Host and Microbe  
The data presented by Loh and colleagues presents the first example of a trans acting SAM riboswitch based on the ability of SreA to bind the 5 0 UTR of prfA and influence protein expression .  ...  Figure 1 . 1 Model of SreA cis and trans Regulation (A) The SreA riboswitch is located immediately upstream of three genes, lmo2491-2418-2417.  ... 
doi:10.1016/j.chom.2009.10.009 pmid:19917494 fatcat:7ohlskzht5fcbkqcpgtha2k4uu

Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes

Harald H H Göring, Joanne E Curran, Matthew P Johnson, Thomas D Dyer, Jac Charlesworth, Shelley A Cole, Jeremy B M Jowett, Lawrence J Abraham, David L Rainwater, Anthony G Comuzzie, Michael C Mahaney, Laura Almasy (+5 others)
2007 Nature Genetics  
Linkage analysis uncovered 41,000 cis-regulated transcripts at a false discovery rate of 5% and showed that the expression quantitative trait loci with the most significant linkage evidence are often located  ...  Although environmental stimuli may influence the location, timing, and/or level of transcription of specific genes, genetic differences among individuals are also known to have a significant role.  ...  The SOLAR statistical genetics computer package is supported by a grant from the US National Institute of Mental Health (MH059490).  ... 
doi:10.1038/ng2119 pmid:17873875 fatcat:vjuzndcgnfctpa7gimbaeoxeti
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