ABSTRACT
The human genome folds to create thousands of intervals, called "contact domains," that exhibit enhanced contact frequency within themselves. "Loop domains" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. "Compartment domains" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation of each loop. Although re-formation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid.
Subject(s)
Cell Cycle Proteins/metabolism , Cell Nucleus/genetics , Chromosomal Proteins, Non-Histone/metabolism , Chromosomes/metabolism , Genome, Human , Repressor Proteins/metabolism , CCCTC-Binding Factor , Cell Line, Tumor , DNA-Binding Proteins , Enhancer Elements, Genetic , Histone Code , Humans , Nuclear Proteins/metabolism , Nucleosomes/metabolism , Phosphoproteins/metabolism , CohesinsABSTRACT
SUMMARY: igv.js is an embeddable JavaScript implementation of the Integrative Genomics Viewer (IGV). It can be easily dropped into any web page with a single line of code and has no external dependencies. The viewer runs completely in the web browser, with no backend server and no data pre-processing required. AVAILABILITY AND IMPLEMENTATION: The igv.js JavaScript component can be installed from NPM at https://www.npmjs.com/package/igv. The source code is available at https://github.com/igvteam/igv.js under the MIT open-source license. IGV-Web, the end-user application built around igv.js, is available at https://igv.org/app. The source code is available at https://github.com/igvteam/igv-webapp under the MIT open-source license. SUPPLEMENTARY INFORMATION: Supplementary information is available at Bioinformatics online.
Subject(s)
Genomics , Software , Web BrowserABSTRACT
An amendment to this paper has been published and can be accessed via the original article.
ABSTRACT
Advances in the study of chromosome conformation capture technologies, such as Hi-C technique - capable of capturing chromosomal interactions in a genome-wide scale - have led to the development of three-dimensional chromosome and genome structure reconstruction methods from Hi-C data. The three dimensional genome structure is important because it plays a role in a variety of important biological activities such as DNA replication, gene regulation, genome interaction, and gene expression. In recent years, numerous Hi-C datasets have been generated, and likewise, a number of genome structure construction algorithms have been developed.In this work, we outline the construction of a novel Genome Structure Database (GSDB) to create a comprehensive repository that contains 3D structures for Hi-C datasets constructed by a variety of 3D structure reconstruction tools. The GSDB contains over 50,000 structures from 12 state-of-the-art Hi-C data structure prediction algorithms for 32 Hi-C datasets.GSDB functions as a centralized collection of genome structures which will enable the exploration of the dynamic architectures of chromosomes and genomes for biomedical research. GSDB is accessible at http://sysbio.rnet.missouri.edu/3dgenome/GSDB.
Subject(s)
Chromosomes/genetics , Databases, Genetic , Genome , Algorithms , Nucleic Acid Conformation , Principal Component AnalysisABSTRACT
Contact mapping experiments such as Hi-C explore how genomes fold in 3D. Here, we introduce Juicebox.js, a cloud-based web application for exploring the resulting datasets. Like the original Juicebox application, Juicebox.js allows users to zoom in and out of such datasets using an interface similar to Google Earth. Juicebox.js also has many features designed to facilitate data reproducibility and sharing. Furthermore, Juicebox.js encodes the exact state of the browser in a shareable URL. Creating a public browser for a new Hi-C dataset does not require coding and can be accomplished in under a minute. The web app also makes it possible to create interactive figures online that can complement or replace ordinary journal figures. When combined with Juicer, this makes the entire process of data analysis transparent, insofar as every step from raw reads to published figure is publicly available as open source code.
Subject(s)
Computational Biology/methods , Image Processing, Computer-Assisted/methods , Cloud Computing , Computer Graphics , Computers , Data Analysis , Genome/genetics , Internet , Reproducibility of Results , SoftwareABSTRACT
The Integrative Genomics Viewer (IGV) for iPad, based on the popular IGV application for desktop and laptop computers, supports researchers who wish to take advantage of the mobility of today's tablet computers to view genomic data and present findings to colleagues.