Chromatin three-dimensional interactions mediate genetic effects on gene expression

Article Article scientifique Article Chromatin three-dimensional interactions mediate genetic effects on gene expression eng 2019 author Delaneau Olivier 810945 author Zazhytska M author Borel Christelle 514149 author Giannuzzi G author Rey Guillaume 725242 author Howald Cédric 510669 author Kumar S author Ongen Halit 744747 author Popadin Konstantin 736361 author Marbach D author Ambrosini G author Bielser D author Hacker D author Romano Luciana 134901 author Ribaux Pascale Garlonne 543255 author Wiederkehr M author Falconnet Emilie 656349 author Bucher P author Bergmann S author Antonarakis Stylianos 22813 author Reymond A author Dermitzakis Emmanouil 542683 10.1126/science.aat8266 31048460 0036-8075 Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression, and genetic variants across 317 individuals and two cell types. We show that variability in regulatory activity is structured at the intra- and interchromosomal levels within 12,583 cis-regulatory domains and 30 trans-regulatory hubs that highly reflect the local (that is, topologically associating domains) and global (that is, open and closed chromatin compartments) nuclear chromatin organization. These structures delimit cell type-specific regulatory networks that control gene expression and coexpression and mediate the genetic effects of cis- and trans-acting regulatory variants on genes. Supplémental datasets: ftp://ftp.1000genomes.ebi.ac.uk/vol1/ftp/release/20130502/ and ftp://ftp.1000genomes.ebi.ac.uk/vol1/ftp/technical/working/20120131_omni_genotypes_and_intensities/ Chromatin/chemistry/metabolism Gene Expression Regulation Genetic Variation Genome Human Humans Quantitative Trait Loci Regulatory Elements Transcriptional Dewey 590 Dewey 576.5 Swiss National Science Foundation The effect of sequence variation on chromatin structure and transcription 130326 CH Programmes Swiss National Science Foundation Elucidating the effects of germ-line and somatic regulatory DNA sequence variants in health and disease 170096 CH Project funding Swiss National Science Foundation Assessing the impact of copy number variants 160203 CH Project funding Swiss National Science Foundation Chromosome 21: functional genomics and molecular pathophysiology of trisomy 21 163180 CH Projects 23 Institut de génétique et de génomique 0DH 135 Département de médecine génétique et développement 21D false 551 Population Genomics and Genetics of Complex Traits 892 https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3656/ https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3657/ https://www.ebi.ac.uk/ega/studies/EGAS00001003485 https://zenodo.org/record/2572871 https://zenodo.org/record/2536039 Science 364 6439 739ed77a-9976-43ed-89ff-c740e70686b2 Article (Published version) Restricted eaat8266.full.pdf 2382398 application/pdf 4c5564f9-c12e-429d-84a1-fdb72cb0e56d Supplemental data Restricted aat8266_Delaneau_SM.pdf 6190437 application/pdf restrictedAccess Centres et instituts / Institut de génétique et de génomique Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

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Chromatin three-dimensional interactions mediate genetic effects on gene expression	Science			2019	363	2

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Rey, Guillaume