Cellular levels of signaling factors are sensed by β-actin alleles to modulate transcriptional pulse intensity

Alon Kalo, Itamar Kanter, Amit Shraga, Jonathan Sheinberger, Hadar Tzemach, Noa Kinor, Robert H. Singer, Timothée Lionnet, Yaron Shav-Tal

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The transcriptional response of β-actin to extra-cellular stimuli is a paradigm for transcription factor complex assembly and regulation. Serum induction leads to a precisely timed pulse of β-actin transcription in the cell population. Actin protein is proposed to be involved in this response, but it is not known whether cellular actin levels affect nuclear β-actin transcription. We perturbed the levels of key signaling factors and examined the effect on the induced transcriptional pulse by following endogenous β-actin alleles in single living cells. Lowering serum response factor (SRF) protein levels leads to loss of pulse integrity, whereas reducing actin protein levels reveals positive feedback regulation, resulting in elevated gene activation and a prolonged transcriptional response. Thus, transcriptional pulse fidelity requires regulated amounts of signaling proteins, and perturbations in factor levels eliminate the physiological response, resulting in either tuning down or exaggeration of the transcriptional pulse.

Original languageEnglish (US)
Pages (from-to)419-432
Number of pages14
JournalCell Reports
Volume11
Issue number3
DOIs
StatePublished - Apr 21 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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