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Published online before print August 18, 2005
Genome Research, DOI: 10.1101/gr.3873705
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Genome Research Vol 0, Issue 2005, gr.3873705, 2005
© 2005 Cold Spring Harbor Laboratory Press

Letter

ATG deserts define a novel core promoter subclass

Maxwell P. Lee2,3, Kevin Howcroft3,4, Aparna Kotekar1, Howard H. Yang2, Kenneth H. Buetow2 and Dinah S. Singer1,5

1 Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA , 2 Laboratory of Population Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA

The MHC class I gene, PD1, has neither functional TATAA nor Initiator (Inr) elements in its core promoter and initiates transcription at multiple, dispersed sites over an extended region in vitro. Here, we define a novel core promoter feature that supports regulated transcription through selective transcription start site (TSS) usage. We demonstrate that TSS selection is actively regulated and context dependent. Basal and activated transcriptions initiate from largely nonoverlapping TSS regions. Transcripts derived from multiple TSS encode a single protein, due to the absence of any ATG triplets within ~430 bp upstream of the major transcription start site. Thus, the PD1 core promoter is embedded within an "ATG desert."; Remarkably, extending this analysis genome-wide, we find that ATG deserts define a novel promoter subclass. They occur nonrandomly, are significantly associated with non-TATAA promoters that use multiple TSS, independent of the presence of CpG islands (CGI). We speculate that ATG deserts may provide a core promoter platform upon which complex upstream regulatory signals can be integrated, targeting multiple TSS whose products encode a single protein.


[Supplemental material is available online at www.genome.org.]

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.3873705. Article published online before print in August 2005.

3 These two authors contributed equally to this work.

4 Present address: Cancer Immunology and Hematology Branch, Division of Cancer Biology, Bethesda, MD 20892.

5 Corresponding author.
E-mail dinah.singer{at}nih.gov; fax (301) 480-8499.


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