6533b85cfe1ef96bd12bc04a

RESEARCH PRODUCT

Direct observation of frequency modulated transcription in single cells using light activation

Xiuhau MengDaniel R. LarsonLiang SunDavid S. LawrenceChristoph FritzschRobert H. Singer

subject

LightTranscription GeneticQH301-705.5SciencePopulationGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciences0302 clinical medicineTranscription (biology)transcription factorsGene expressionHumansRNA MessengerBiology (General)educationGeneTranscription factortranscription factor030304 developmental biologyRegulation of gene expressionTranscriptional burstingGenetics0303 health scienceseducation.field_of_studyGeneral Immunology and MicrobiologyChemistryGeneral NeuroscienceQRRNAGeneral MedicineBiophysics and Structural BiologyCell biologyGenes and Chromosomesgene expressionMedicinesingle-moleculefluorescence030217 neurology & neurosurgeryResearch ArticleHuman

description

Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated gene activation. We determine that steroids drive mRNA synthesis by frequency modulation of transcription. This digital behavior in single cells gives rise to the well-known analog dose response across the population. To test this model, we developed a light-activation technology to turn on a single steroid-responsive gene and follow dynamic synthesis of RNA from the activated locus. DOI: http://dx.doi.org/10.7554/eLife.00750.001

yearjournalcountryeditionlanguage
2013-09-01eLife
https://doi.org/10.7554/elife.00750