Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells.
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.
Hu
Jianzhong
J
Department of Microbiology, Mount Sinai School of Medicine, New York 10029, USA.
Sealfon
Stuart C
SC
Hayot
Fernand
F
Jayaprakash
Ciriyam
C
Kumar
Madhu
M
Pendleton
Audrey C
AC
Ganee
Arnaud
A
Fernandez-Sesma
Ana
A
Moran
Thomas M
TM
Wetmur
James G
JG
D000483:Alleles; D002478:Cells, Cultured; D002877:Chromosomes, Human / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D008957:Models, Genetic; D009522:Newcastle disease virus / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis; D013269:Stochastic Processes; D015533:Transcriptional Activation
D012333:RNA, Messenger; D012367:RNA, Viral; D016899:Interferon-beta