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 language | English |
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Pages (from-to) | 419-432 |
Number of pages | 14 |
Journal | Cell Reports |
Volume | 11 |
Issue number | 3 |
DOIs | |
State | Published - 21 Apr 2015 |
Bibliographical note
Publisher Copyright:© 2015 The Authors.
Funding
We thank Gur Yaari (BIU Faculty of Engineering) for guidance with mathematical modeling. This work was supported by the United States-Israel Binational Science Foundation (Y.S.-T. and R.H.S.), the European Research Council (Y.S.-T.), NIH/NINDS grant 9R01NS083085-20 (R.H.S.), and Howard Hughes Medical Institute (T.L.).
Funders | Funder number |
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National Institute of Neurological Disorders and Stroke | R01NS083085 |
United States-Israel Binational Science Foundation |