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 alpha-globin locus in K562 cells. ADHM provides 
a powerful approach to identifying DNaseI hypersensitive sites across large 
genomic regions.