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Nucleic Acids Research Advance Access originally published online on August 2, 2007
Nucleic Acids Research 2007 35(15):5232-5241; doi:10.1093/nar/gkm557
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Nucleic Acids Research, 2007, Vol. 35, No. 15 5232-5241
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells

Jianzhong Hu1, Stuart C. Sealfon2,3, Fernand Hayot2,3, Ciriyam Jayaprakash4, Madhu Kumar1, Audrey C. Pendleton1, Arnaud Ganee1, Ana Fernandez-Sesma1,3, Thomas M. Moran1,3 and James G. Wetmur1,3,*

1Department of Microbiology, Mount Sinai School of Medicine, 2Department of Neurology, Mount Sinai School of Medicine, New York 10029 USA, 3Center for Translational Systems Biology, Mount Sinai School of Medicine and 4Department of Physics, Ohio State University, Columbus, Ohio 43210, USA

*To whom correspondence should be addressed. Email: james.wetmur{at}mssm.edu

Received May 1, 2007. Revised July 2, 2007. Accepted July 7, 2007.

The induction of interferon beta (IFNB1) is a key event in the antiviral immune response. We studied the role of transcriptional noise in the regulation of the IFNB1 locus in primary cultures of human dendritic cells (DCs), which are important ‘first responders’ to viral infection. In single cell assays, IFNB1 mRNA expression in virus-infected DCs showed much greater cell-to-cell variation than that of a housekeeping gene, another induced transcript and viral RNA. We determined the contribution of intrinsic noise by measuring the allelic origin of transcripts in each cell and found that intrinsic noise is a very significant part of total noise. We developed a stochastic model to investigate the underlying mechanisms. We propose that the surprisingly high levels of IFNB1 transcript noise originate from the complexity of IFNB1 enhanceosome formation, which leads to a range up to many minutes in the differences within each cell in the time of activation of each allele.


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