Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites

George A. Follows, Pawan Dhami, Berthold Göttgens, Alexander W. Bruce, Peter J. Campbell, Shane C. Dillon, Aileen M. Smith, Christoph Koch, Ian J. Donaldson, Mike A. Scott, Ian Dunham, Mary E. Janes, David Vetrie, Anthony R. Green

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The identification of cis-regulatory elements is central to understanding gene transcription. Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements. Traditional methods used to identify DNaseI hypersensitive sites are cumbersome and can only be applied to short stretches of DNA at defined locations. Here we report the development of a novel genomic array-based approach to DNaseI hypersensitive site mapping (ADHM) that permits precise, large-scale identification of such sites from as few as 5 million cells. Using ADHM we identified all previously recognized hematopoietic regulatory elements across 200 kb of the mouse T-cell acute lymphocytic leukemia-1 (Tal1) locus, and, in addition, identified two novel elements within the locus, which show transcriptional regulatory activity. We further validated the ADHM protocol by mapping the DNaseI hypersensitive sites across 250 kb of the human TAL1 locus in CD34+ primary stem/progenitor cells and K562 cells and by mapping the previously known DNaseI hypersensitive sites across 240 kb of the human α-globin locus in K562 cells. ADHM provides a powerful approach to identifying DNaseI hypersensitive sites across large genomic regions. ©2006 by Cold Spring Harbor Laboratory Press.
    Original languageEnglish
    Pages (from-to)1310-1319
    Number of pages9
    JournalGenome research
    Volume16
    Issue number10
    DOIs
    Publication statusPublished - 2006

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