title: Cellular Levels of Signaling Factors Are Sensed by β-actin Alleles to Modulate Transcriptional Pulse Intensity.
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.
authors: The Mina and Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan 5290002, Israel.
authors: Alon
authors: A
authors: Kalo
authors: The Mina and Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan 5290002, Israel.
authors: Itamar
authors: I
authors: Kanter
authors: The Mina and Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan 5290002, Israel.
authors: Amit
authors: A
authors: Shraga
authors: The Mina and Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan 5290002, Israel.
authors: Jonathan
authors: J
authors: Sheinberger
authors: The Mina and Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan 5290002, Israel.
authors: Hadar
authors: H
authors: Tzemach
authors: The Mina and Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan 5290002, Israel.
authors: Noa
authors: N
authors: Kinor
authors: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Transcription Imaging Consortium, Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA 20147, USA; Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Robert H
authors: RH
authors: Singer
authors: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Transcription Imaging Consortium, Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA 20147, USA.
authors: Timothée
authors: T
authors: Lionnet
authors: The Mina and Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan 5290002, Israel. Electronic address: yaron.shav-tal@biu.ac.il.
authors: Yaron
authors: Y
authors: Shav-Tal
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics*; D000483:Alleles; D000818:Animals; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D034741:RNA, Small Interfering; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D000199:Actins; D034741:RNA, Small Interfering; D026362:Serum Response Factor