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The Three-Dimensional Architecture of a Bacterial Genome and Its Alteration by Genetic Perturbation

Mark A. Umbarger, Esteban Toro, Matthew A. Wright, Gregory J. Porreca, Davide Baù, Sun-Hae Hong, Michael J. Fero, Lihua J. Zhu, Marc A. Marti-Renom, Harley H. McAdams, Lucy Shapiro, Job Dekker (+1 others)
2011 Molecular Cell  
We have determined the three-dimensional (3D) architecture of the Caulobacter crescentus genome by combining genome-wide chromatin interaction detection, live-cell imaging, and computational modeling.  ...  Modeling was conceived of by MAM-R, JD, and DB, and was performed by MAU, MAW, and DB with support from MAM-R.  ...  MAM-R and DB were funded by the Spanish Ministerio de Ciencia e Innovación (BIO2007/66670 and BFU2010/19310) and JD was supported by a grant from the National Institutes of Health (HG003143) and a W.M.  ... 
doi:10.1016/j.molcel.2011.09.010 pmid:22017872 pmcid:PMC3874842 fatcat:ly2brlvdlrfx5dg6qbcdlreo74

Peering deeper into the transcriptome

Tal Nawy
2012 Nature Methods  
The three-dimensional architecture of a bacterial genome and its alteration by genetic perturbation. Mol. Cell 44, 252-264 (2011). tal nawy ReseaRch PaPeRs Mercer, T.R. et al.  ...  A 3D map of a bacterial chromosome. Chromosome arms are shown in orange and yellow. Image courtesy of J. Dekker.  ... 
doi:10.1038/nmeth.1844 pmid:22312630 fatcat:7rf46xbdmzd4lixom4pophk7ee

Functional Genomics of Host–Microbiome Interactions in Humans

Francesca Luca, Sonia S. Kupfer, Dan Knights, Alexander Khoruts, Ran Blekhman
2018 Trends in Genetics  
We argue that, similar to human GWAS, it is important to use functional genomics techniques to gain a mechanistic understanding of causal host-microbiome interactions and its role in human disease.  ...  Recent genome-wide association studies (GWAS) have used microbiome variation as a complex trait, and have uncovered human genetic variants that are associated with the microbiome.  ...  The application of in vitro models for interrogation of the genomic architecture of host-microbiome interactions is limited by the fact that cell lines are transformed and malignant (e.g., Caco2) and thus  ... 
doi:10.1016/j.tig.2017.10.001 pmid:29107345 pmcid:PMC5774629 fatcat:5lx7o4bfxvgspkxkcxrihm23wq

Systems genetic discovery of host-microbiome interactions reveals mechanisms of microbial involvement in disease [article]

Jason Bubier, Vivek Philip, Christopher Quince, James Campbell, Yanjiao Zhou, Tatiana Vishnivetskaya, Suman Duvvuru, Rachael Hageman Blair, Juliet Ndukum, Kevin D Donohue, Charles Phillips, Carmen Foster (+9 others)
2018 bioRxiv   pre-print
The role of the microbiome in health and disease involves complex networks of host genetics, genomics, microbes and environment.  ...  To examine the interplay among the whole host genome, transcriptome and microbiome, we mapped quantitative trait loci and correlated the abundance of cecal mRNA, luminal microflora, physiology and behavior  ...  Detecting a QTL for Enterorohabdus abundance and relating it to genetic regulation of Trafd1 abundance enabled us to hypothesize and ultimately demonstrate that perturbation of Trafd1 influences social  ... 
doi:10.1101/349605 fatcat:3lrj5rdvszfdbkusikrdyu7aua

Integrating systems biology data to yield functional genomics insights

Polly Fordyce, Nicholas Ingolia
2011 Genome Biology  
Abstract A report of the recent EMBO Conference 'From Functional Genomics to Systems Biology' held at the EMBL Advanced Training Centre,  ...  Powered by advances in DNA sequencing, high-resolution maps of genome-wide trans cription factor and chromatin occupancy data have begun to shed light on the basic mechanisms that regu late gene expression  ...  Three-dimensional chromosome structure and interactions with regulatory proteins Studies of three-dimensional chromosomal conformations revealed a complex architecture, with widespread interactions both  ... 
doi:10.1186/gb-2011-12-1-302 pmid:21247510 pmcid:PMC3091297 fatcat:abzuj5cbezettkneiirdz7i27u

A Holling Functional Response Model for Mapping QTLs Governing Interspecific Interactions

Xiao-Yu Zhang, Huiying Gong, Qing Fang, Xuli Zhu, Libo Jiang, Rongling Wu
2021 Frontiers in Genetics  
This model provides a quantitative means of predicting the genetic architecture that shapes the dynamic behavior of ecological communities.  ...  By applying the new model to a published mapping data from a competition experiment of two microbial species, we identify a set of previously uncharacterized QTLs that are specifically responsible for  ...  Mapping the Two-Dimensional Genetic Architecture of Microbial Growth in Co-culture Unlike a case of monoculture in which the phenotype of a species is only controlled by its own genes, the growth of one  ... 
doi:10.3389/fgene.2021.766372 pmid:34721549 pmcid:PMC8554200 fatcat:jcx6z2bacvf2ngpgsxxidw5fca

Genome-Wide Association Studies In Plant Pathosystems: Toward an Ecological Genomics Approach

Claudia Bartoli, Fabrice Roux
2017 Frontiers in Plant Science  
an unbiased picture of the genetic architecture driving disease resistance.  ...  For example, agricultural practices can drastically alter the environment by offering routes for transmission of pathogens (Institute of Medicine, 2003) .  ...  Copyright © 2017 Bartoli and Roux. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).  ... 
doi:10.3389/fpls.2017.00763 pmid:28588588 pmcid:PMC5441063 fatcat:jcw2xklz4remjklmcxmr7a3zz4

From structure to function of bacterial chromosomes: Evolutionary perspectives and ideas for new experiments

Marco Cosentino Lagomarsino, Olivier Espéli, Ivan Junier
2015 FEBS Letters  
Toward this end, we first provide a brief overview of experimental tools that have provided insights into the description of the bacterial chromosome, including genetic, biochemical and fluorescence microscopy  ...  The link between chromosome structure and function is a challenging open question because chromosomes in vivo are highly dynamic and arduous to manipulate.  ...  Moreover, the exploration of the alterations to chromosome architecture through perturbations such as the deletion of architectural genes or artificially induced genome reorganization is complicated by  ... 
doi:10.1016/j.febslet.2015.07.002 pmid:26171924 fatcat:qjrdua53pbhylgcliudv73qjlq

The 4D nucleome project

Job Dekker, Andrew S. Belmont, Mitchell Guttman, Victor O. Leshyk, John T. Lis, Stavros Lomvardas, Leonid A. Mirny, Clodagh C. O'Shea, Peter J. Park, Bing Ren, Joan C. Ritland Politz, Jay Shendure (+1 others)
2017 Nature  
Preface The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic understanding  ...  of how the nucleus is organized and functions.  ...  Together these integrated studies promise to allow moving from a one-dimensional representation of the genome as a long DNA sequence to a spatially and dynamically organized three dimensional structure  ... 
doi:10.1038/nature23884 pmid:28905911 pmcid:PMC5617335 fatcat:ig6dcvkkbnebhc73g2ii3wldk4

The Dynamic Architectural and Epigenetic Nuclear Landscape: Developing the Genomic Almanac of Biology and Disease

Phillip W.L. Tai, Sayyed K. Zaidi, Hai Wu, Rodrigo A. Grandy, Martin Montecino, André J. van Wijnen, Jane B. Lian, Gary S. Stein, Janet L. Stein
2014 Journal of Cellular Physiology  
sequencing methodologies have drastically changed how we currently understand epigenetic gene control within the context of three-dimensional nuclear structure.  ...  For decades, experimental limitations to study the structural organization of the interphase nucleus restricted our understanding of its contributions towards gene regulation and disease.  ...  Himeda for critical reading of the manuscript, and J. Diaz for editorial assistance with preparation of the manuscript.  ... 
doi:10.1002/jcp.24508 pmid:24242872 pmcid:PMC3996806 fatcat:rx4tof4r7zcjrnti44eatwlh2q

Systems genetics approaches to understand complex traits

Mete Civelek, Aldons J. Lusis
2013 Nature reviews genetics  
Acknowledgements The authors thank R. Chen for assistance in the preparation of this paper. M.C. is supported by Ruth L.  ...  Kirschstein National Research Service Award T32HL69766; A.J.L. is supported by the US National Institutes of Health grants HL30568, HL28481, HL094322, HL110667 and DP3D094311, and Transatlantic Networks  ...  The advantage of this systems genetics approach is that it allows an analysis of molecular interactions in a context that is the most relevant to the clinical trait, namely, multiple genetic perturbations  ... 
doi:10.1038/nrg3575 pmid:24296534 pmcid:PMC3934510 fatcat:pinns2wz3bh3zjn3pjkxzcrtva

The contribution of non-coding regulatory elements to cardiovascular disease

Diego Villar, Stephanie Frost, Panos Deloukas, Andrew Tinker
2020 Open Biology  
Genome-wide association studies across a range of cardiovascular traits and pathologies have highlighted the prevalence of common non-coding genetic variants within candidate loci.  ...  Here, we review genetic, epigenomic and molecular approaches to investigate the contribution of non-coding regulatory elements in cardiovascular biology.  ...  This work has been funded by the British Heart Foundation (Fellowship FS/18/39/33684 to D.V.) and Queen Mary University of London.  ... 
doi:10.1098/rsob.200088 pmid:32603637 fatcat:pwja6c6y4rdqxlqbxaz3w55lx4

Fighting change with change: adaptive variation in an uncertain world

Lauren Ancel Meyers, James J. Bull
2002 Trends in Ecology & Evolution  
Environmental perturbations move the ball along the surface whereas genetic perturbations alter the topography.  ...  *Although genetic mutations alter the genome per se, mutators often produce a cloud of genotypes focused around a wild type.  ... 
doi:10.1016/s0169-5347(02)02633-2 fatcat:nhfev2zumrbybgqu2dolum4nhu

CRISPR Screens in Toxicology Research: An Overview

Amin Sobh, Max Russo, Christopher D. Vulpe
2021 Current Protocols  
The use of genome editing tools is expanding our understanding of various human diseases by providing insight into gene-disease interactions.  ...  genome editing to the study of toxicants could help in the identification of novel gene-environment interactions.  ...  Genome-wide alterations in gene expression associated with each genetic perturbation in a pool can be determined by single-cell RNA sequencing (scRNA-Seq), and this approach is referred to as perturbseq  ... 
doi:10.1002/cpz1.136 pmid:34043288 fatcat:ewiray4e3jhj5anacuq5kdhyze

Using CRISPR to understand and manipulate gene regulation

Ersin Akinci, Marisa C Hamilton, Benyapa Khowpinitchai, Richard I Sherwood
2021 Development  
Understanding how genes are expressed in the correct cell types and at the correct level is a key goal of developmental biology research.  ...  CRISPR-Cas9 has begun to transform the study of gene regulation, allowing for precise manipulation of genomic sequences, epigenetic functionalization and gene expression.  ...  Funding The authors acknowledge funding from the National Institutes of Health (R01HG008754, R21HG010391), American Cancer Society, American Heart Association, National Organization for Rare Disorders,  ... 
doi:10.1242/dev.182667 pmid:33913466 pmcid:PMC8126405 fatcat:dk2xmek6vjhybfzax4ouh5lmau
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