Mapping Native R-Loops Genome-wide Using a Targeted Nuclease Approach.

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  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Cambridge, MA] : Cell Press, c 2012-
    • Subject Terms:
      Genome, Human* ; R-Loop Structures*; Deoxyribonucleases/*metabolism; Antibodies/metabolism ; Cell Line ; Enhancer Elements, Genetic/genetics ; HEK293 Cells ; Humans ; Recombinant Proteins/metabolism ; Ribonuclease H/metabolism ; Tandem Repeat Sequences/genetics
    • Abstract:
      R-loops are three-stranded DNA:RNA hybrids that are implicated in many nuclear processes. While R-loops may have physiological roles, the formation of stable, aberrant R-loops has been observed in neurological disorders and cancers. Current methods to assess their genome-wide distribution rely on affinity purification, which is plagued by large input requirements, high noise, and poor sensitivity for dynamic R-loops. Here, we present MapR, a method that utilizes RNase H to guide micrococcal nuclease to R-loops, which are subsequently cleaved, released, and identified by sequencing. MapR detects R-loops formed at promoters and active enhancers that are likely to form transient R-loops due to the low transcriptional output of these regulatory elements and the short-lived nature of enhancer RNAs. MapR is as specific as existing techniques and more sensitive, allowing for genome-wide coverage with low input material in a fraction of the time.
      (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
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    • Grant Information:
      DP2 NS105576 United States NS NINDS NIH HHS; P30 CA010815 United States CA NCI NIH HHS; R01 GM127408 United States GM NIGMS NIH HHS; T32 HG000046 United States HG NHGRI NIH HHS
    • Contributed Indexing:
      Keywords: DNA:RNA hybrids; R-loops; chromatin; gene expression; transcription
    • Accession Number:
      0 (Antibodies)
      0 (Recombinant Proteins)
      EC 3.1.- (Deoxyribonucleases)
      EC 3.1.26.4 (Ribonuclease H)
    • Publication Date:
      Date Created: 20191031 Date Completed: 20200925 Latest Revision: 20240607
    • Publication Date:
      20240607
    • Accession Number:
      PMC6870988
    • Accession Number:
      10.1016/j.celrep.2019.09.052
    • Accession Number:
      31665646