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Activity-by-contact model of enhancer-promoter regulation from thousands of CRISPR perturbations.
Fulco, Charles P; Nasser, Joseph; Jones, Thouis R; Munson, Glen; Bergman, Drew T; Subramanian, Vidya; Grossman, Sharon R; Anyoha, Rockwell; Doughty, Benjamin R; Patwardhan, Tejal A; Nguyen, Tung H; Kane, Michael; Perez, Elizabeth M; Durand, Neva C; Lareau, Caleb A; Stamenova, Elena K; Aiden, Erez Lieberman; Lander, Eric S; Engreitz, Jesse M.
Afiliação
  • Fulco CP; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Nasser J; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Jones TR; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Munson G; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bergman DT; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Subramanian V; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Grossman SR; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Anyoha R; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Doughty BR; Department of Biology, MIT, Cambridge, MA, USA.
  • Patwardhan TA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Nguyen TH; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kane M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Perez EM; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Durand NC; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lareau CA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Stamenova EK; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Aiden EL; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA.
  • Lander ES; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Engreitz JM; Department of Computer Science and Department of Computational and Applied Mathematics, Rice University, Houston, TX, USA.
Nat Genet ; 51(12): 1664-1669, 2019 12.
Article em En | MEDLINE | ID: mdl-31784727
ABSTRACT
Enhancer elements in the human genome control how genes are expressed in specific cell types and harbor thousands of genetic variants that influence risk for common diseases1-4. Yet, we still do not know how enhancers regulate specific genes, and we lack general rules to predict enhancer-gene connections across cell types5,6. We developed an experimental approach, CRISPRi-FlowFISH, to perturb enhancers in the genome, and we applied it to test >3,500 potential enhancer-gene connections for 30 genes. We found that a simple activity-by-contact model substantially outperformed previous methods at predicting the complex connections in our CRISPR dataset. This activity-by-contact model allows us to construct genome-wide maps of enhancer-gene connections in a given cell type, on the basis of chromatin state measurements. Together, CRISPRi-FlowFISH and the activity-by-contact model provide a systematic approach to map and predict which enhancers regulate which genes, and will help to interpret the functions of the thousands of disease risk variants in the noncoding genome.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Elementos Facilitadores Genéticos / Regiões Promotoras Genéticas / Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Elementos Facilitadores Genéticos / Regiões Promotoras Genéticas / Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos