Discovery of gene regulatory elements through a new bioinformatics analysis of haploid genetic screens.

Autor: Patel BB; Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.; Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America., Lebensohn AM; Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.; Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America., Pusapati GV; Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America., Carette JE; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America., Salzman J; Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, California, United States of America., Rohatgi R; Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.; Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Jan 29; Vol. 14 (1), pp. e0198463. Date of Electronic Publication: 2019 Jan 29 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0198463
Abstrakt: The systematic identification of regulatory elements that control gene expression remains a challenge. Genetic screens that use untargeted mutagenesis have the potential to identify protein-coding genes, non-coding RNAs and regulatory elements, but their analysis has mainly focused on identifying the former two. To identify regulatory elements, we conducted a new bioinformatics analysis of insertional mutagenesis screens interrogating WNT signaling in haploid human cells. We searched for specific patterns of retroviral gene trap integrations (used as mutagens in haploid screens) in short genomic intervals overlapping with introns and regions upstream of genes. We uncovered atypical patterns of gene trap insertions that were not predicted to disrupt coding sequences, but caused changes in the expression of two key regulators of WNT signaling, suggesting the presence of cis-regulatory elements. Our methodology extends the scope of haploid genetic screens by enabling the identification of regulatory elements that control gene expression.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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