Peter J. Sabo *, Richard Humbert *, Michael Hawrylycz *, James C. Wallace *, Michael O. Dorschner *, Michael McArthur , and John A. Stamatoyannopoulos * ^@

*Department of Molecular Biology, Regulome, Canal View Building, 551 North 34th Street, Seattle, WA 98103; and Regulome UK, Norwich Research Park, Norwich NR4 7UH, United Kingdom

^@ To whom correspondence should be addressed.
John A. Stamatoyannopoulos , E-mail:   jstam@regulome.com

Comprehensive identification of sequences that regulate transcription is one of the major goals of genome biology. Focal alteration in chromatin structure in vivo, detectable through hypersensitivity to DNaseI and other nucleases, is the sine qua non of a diverse cast of transcriptional regulatory elements including enhancers, promoters, insulators, and locus control regions. We developed an approach for genome-scale identification of DNase-I hypersensitive sites (HSs) via isolation and cloning of in vivo DNase-I cleavage sites to create libraries of active chromatin sequences (ACSs). Here, we describe analysis of >61,000 ACSs derived from erythroid cells. We observed peaks in the density of ACSs at the transcriptional start sites of known genes at non-gene-associated CpG islands, and, to a lesser degree, at evolutionarily conserved noncoding sequences. Peaks in ACS density paralleled the distribution of DNase-I HSs. ACSs and DNase-I HSs were distributed between both expressed and nonexpressed genes, suggesting that a large proportion of genes reside within open
chromatin domains. The results permit a quantitative approximation of the distribution of HSs and classical cis-regulatory sequences in the human genome.

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3. Frenster JH, and Hovsepian JA,  "Overshoot in Late Telophase for RNA Re-Programming of Mitotic Chromatin",  RNA 2003, 211 (2003).

4. Frenster JH, "Yeast  RNA  Re-Programming  of  Already-Active  Mammalian Chromatin".  RNA 2002, 592 (2002).

5. Frenster JH, "Activation of DNA Transcription within Repressed Chromatin by Nuclear RNA Species",    RNA 2001, 237 (2001).

6. Hovsepian JA, and Frenster JH, "RNA-Induced Melting of DNA during Selective Gene Transcription",
Molec. Biol. Cell, vol. 13, supp. p. 239a (November, 2002).
 

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Reviews and Research:

Links to Euchromatin Activator RNA Reviews:
Links to Euchromatin Activator RNA Research:
Links to Ultrastructural Probes of DNase I-Sensitive Sites:
Links to RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma Immuno-Pathology:
Links to Activated T-Lymphocyte Immunotherapy:
Links to Medical Systems Biology:

"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".

For Further Information and Feedback:
E-mail: frenster@euchromatin.net