Simon Cawley ^{1, 5}, Stefan Bekiranov ^{1, 5}, Huck H. Ng ^{2, 3, 4}, Philipp Kapranov ¹, Edward A. Sekinger ² , Dione Kampa ¹, Antonio Piccolboni ¹, Victor Sementchenko ¹, Jill Cheng ¹, Alan J. Williams ¹, Raymond Wheeler ¹, Brant Wong ¹, Jorg Drenkow ¹, Mark Yamanaka ¹, Sandeep Patel ¹, Shane Brubaker ¹, Hari Tammana ¹, Gregg Helt ¹, Kevin Struhl * ^{, 2}, and Thomas R. Gingeras * ^{, 1}

¹ Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051 USA
² Deptartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 USA
³ Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore
⁴ Genome Institute of Singapore, Singapore 138672, Singapore
⁵ These authors contributed equally to the work.

Correspondence:
* Kevin Struhl:    617-432-2104 (phone);     617-432-2529 (fax);
kevin@hms.harvard.edu and
*Thomas R. Gingeras:    408-731-5069 (phone);    408-732-7025 (fax)
tom_gingeras@affymetrix.com

Using high-density oligonucleotide arrays representing essentially all nonrepetitive sequences on human
chromosomes 21 and 22, we map the binding sites in vivo for three DNA binding transcription factors, Sp1,
cMyc, and p53, in an unbiased manner. This mapping reveals an unexpectedly large number of transcription
factor binding site (TFBS) regions, with a minimal estimate of 12,000 for Sp1, 25,000 for cMyc, and 1600 for
p53 when extrapolated to the full genome. Only 22% of these TFBS regions are located at the 5' termini of
protein-coding genes while 36% lie within or immediately 3' to well-characterized genes and are significantly
correlated with noncoding RNAs. A significant number of these noncoding RNAs are regulated in response to
retinoic acid, and overlapping pairs of protein-coding and noncoding RNAs are often coregulated. Thus, the
human genome contains roughly comparable numbers of protein-coding and noncoding genes that are bound by
common transcription factors and regulated by common environmental signals.

1. Boutros M, Kiger AA, Armknecht S, Kerr K, Hild M, Koch B, Haas SA, Heidelberg Fly Array Consortium (Hild M, Beckmann B, Haas S, Koch B, Vingron M, Sauer F, Hoheisel J, and Paro R), Paro R, Perrimon N, "Genome-Wide RNAi Analysis of Growth and Viability in Drosophila Cells".

2. Seitz H, Youngson N, Lin S-P, Dalbert S, Paulsen M, Bachellerie J-P, Ferguson-Smith AC, and Cavaille J, "Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene".

3. Sleutels F, Zwart R, and Barlow DP, "The non-coding Air RNA is required for silencing autosomal imprinted genes".

4. Sleutels F, Tjon G, Ludwig T, and Barlow DP, "Imprinted silencing of Slc22a2 and Slc22a3 does not need transcriptional overlap between Igf2r and Air".

5. Crawford GE, Holt IE, Mulliken JC, Tai D, Blakesly R, Bouffard G, Young A, Masiellot C, Green ED, Wolfsberg TG, and Collins FS, "Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites".

6. Sen G, Wehrman TS, Myers JW, and Blau HM, "Restriction enzyme-generated siRNA (REGS) vectors and libraries".

7. Han M-H, Goud S, Song L, and Fedoroff N, "The Arabidopsis double-stranded RNA-binding protein HYL1 plays a role in microRNA-mediated gene regulation".

8. Lai EC, Wiel C, and Rubin GM, "Complementary miRNA pairs suggest a regulatory role for miRNA:miRNA duplexes".

Further Topics in:  Euchromatin,  active DNA, and  RNA  ribo-regulators:

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".

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