035323fe4a88aea8872eb11de17a3800321cf8e7
galt
  Wed Jan 18 19:59:51 2023 -0800
code cleanup based on htmlCheck output. refs #7914

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-<html>
-<title>UW protein binding footprints</title>
-<body>
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 <h1>Description</h1>
 
 <p>
 The orchestrated binding of transcriptional activators and repressors
 to specific DNA sequences in the context of chromatin defines the
 regulatory program of eukaryotic genomes.  We developed a digital
 approach to assay regulatory protein occupancy on genomic DNA in vivo
 by dense mapping of individual DNase I cleavages from intact nuclei
 using massively parallel DNA sequencing.  Analysis of &gt;23 million
 cleavages across the <i>Saccharomyces cerevisiae</i> genome revealed
 thousands of protected regulatory protein footprints, enabling <i>de
 novo</i> derivation of factor binding motifs as well as the
 identification of hundreds of novel binding sites for major
 regulators.  We observed striking correspondence between
 nucleotide-level DNase I cleavage patterns and protein-DNA
 interactions determined by crystallography.  The data also yielded a
 detailed view of larger chromatin features including positioned
 nucleosomes flanking factor binding regions.  Digital genomic
 footprinting provides a powerful approach to delineate the
 cis-regulatory framework of any organism with an available genome
 sequence. </p>
 
 </ul>
 
 <h1>Display Conventions and Configuration</h1>
 
 <p>
 DNaseI-seq cleavage counts are displayed at nucleotide resolution,
 along with a 'mappability' track that indicates whether tag sequences
 starting at that location on both the forward and the reverse strands can be
 uniquely mapped to the yeast genome.  Finally, the set of footprints
 with q&nbsp;values &lt;0.1 are included, where the q&nbsp;value is
 defined as the minimal false discovery rate threshold at which the
 given footprint is deemed significant.  The name associated with each
 footprint is its q&nbsp;value.</p>
 
 <h1>Methods</h1>
 
 <p>
 To visualize regulatory protein occupancy across the genome of
 <i>Saccharomyces cerevisiae</i>, DNase I digestion of yeast nuclei was
 coupled with massively parallel DNA sequencing to create a dense
 whole-genome map of DNA template accessibility at the 
 nucleotide-level.</p>
 
 <p>
 Yeast nuclei were isolated and treated with a DNase I concentration
 sufficient to release short (&lt;300 bp) DNA fragments.  Small
 fragments were derived from two DNase I "hits" in close proximity.
 Each end of those fragments represents an in vivo DNase I cleavage
 site. The sequence and hence genomic location of these sites were then
 determined by DNA sequencing.</p>
 
 <p>
 Footprints were identified using a computational algorithm that
 evaluates short regions (between 8 and 30 bp) over which the DNase I
 cleavage density was significantly reduced compared with the
 immediately flanking regions.  FDR thresholds were assigned to each
 footprint by comparing p-values obtained from real and shuffled
 cleavage data.</p>
 
 <p>
 Detailed methods are given in Hesselberth <i>et al.</i> (2009), and
 supplementary data and source code are available
 <a href="https://noble.gs.washington.edu/proj/footprinting/" target="_blank">here</a>.</p>
 
 <h1>Credits</h1>
 
 <p>
 This track was produced at the University of Washington by Jay
   R. Hesselberth, Xiaoyu Chen, Zhihong Zhang, Peter J. Sabo, Richard
   Sandstrom, Alex P. Reynolds, Robert E. Thurman, Shane Neph, Michael
   S. Kuehn, William S. Noble (william-noble@u.washington.edu), Stanley
   Fields (fields@u.washington.edu) and John A. Stamatoyannopoulos
   (jstam@stamlab.org).</p>
 
 <h1>References</h1>
 
 <p>
 Hesselberth JR, Chen X, Zhang Z, Sabo PJ, Sandstrom R, Reynolds AP, Thurman RE, Neph S, Kuehn MS,
 Noble WS <em>et al</em>.
 <a href="https://www.nature.com/articles/nmeth.1313"
 target="_blank"> Global mapping of protein-DNA interactions <i>in vivo</i> by digital genomic footprinting</a>.
 <em>Nat Methods</em>. 2009 Apr;6(4):283-9.
 PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/19305407" target="_blank">19305407</a>; PMC: <a
 href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668528/" target="_blank">PMC2668528</a>
 </p>
-</body>
-</html>