scholarly journals Dynamics and heterogeneity of Erk-induced immediate-early gene expression

2021 ◽  
Author(s):  
Siddhartha G. Jena ◽  
Catherine Yu ◽  
Jared E. Toettcher
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Transcriptional Response ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Sequencing Data ◽  
Fixed Tissue ◽  
Erk Activity

SummaryMany canonical signaling pathways exhibit complex time-varying responses, yet how minutes-timescale pulses of signaling interact with the dynamics of transcription and gene expression remains poorly understood. Erk-induced immediate early gene (IEG) expression is a model of this interface, exemplifying both dynamic pathway activity and a rapid, potent transcriptional response. Here, we quantitatively characterize IEG expression downstream of dynamic Erk stimuli in individual cells. We find that IEG expression responds rapidly to acute changes in Erk activity, but only in a sub-population of stimulus-responsive cells. We find that while Erk activity partially predicts IEG expression, a majority of response heterogeneity is independent of Erk and can be rapidly tuned by different mitogenic stimuli and parallel signaling pathways. We extend our findings to an in vivo context, the mouse epidermis, where we observe heterogenous immediate-early gene accumulation in both fixed tissue and single-cell RNA-sequencing data. Our results demonstrate that signaling dynamics can be faithfully transmitted to gene expression and suggest that the signaling-responsive population is an important parameter for interpreting gene expression responses.

In vivo carbon monoxide exposure and hypoxic hypoxia stimulate immediate early gene expression

1997 ◽  
Vol 434 (5) ◽  
pp. 568-574 ◽  
Author(s):  
Bernhard Gess ◽  
Konrad Wolf ◽  
Michael Pfeifer ◽  
Günter A. J. Riegger ◽  
A. Kurtz
Keyword(s):  
Gene Expression ◽  
Carbon Monoxide ◽  
Immediate Early Gene ◽  
Hypoxic Hypoxia ◽  
Early Gene ◽  
Immediate Early ◽  
Early Gene Expression

scholarly journals Protein Kinase Cδ Blocks Immediate-Early Gene Expression in Senescent Cells by Inactivating Serum Response Factor

2004 ◽  
Vol 24 (16) ◽  
pp. 7298-7311 ◽  
Author(s):  
Keith Wheaton ◽  
Karl Riabowol
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Serum Response Factor ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Response Factor ◽  
Serum Response

ABSTRACT Fibroblasts lose the ability to replicate in response to growth factors and become unable to express growth-associated immediate-early genes, including c-fos and egr-1, as they become senescent. The serum response factor (SRF), a major transcriptional activator of immediate-early gene promoters, loses the ability to bind to the serum response element (SRE) and becomes hyperphosphorylated in senescent cells. We identify protein kinase C delta (PKCδ) as the kinase responsible for inactivation of SRF both in vitro and endogenously in senescent cells. This is due to a higher level of PKCδ activity as cells age, production of the PKCδ catalytic fragment, and its nuclear localization in senescent but not in low-passage-number cells. The phosphorylation of T160 of SRF by PKCδ in vitro and in vivo led to loss of SRF DNA binding activity. Both the PKCδ inhibitor rottlerin and ectopic expression of a dominant negative form of PKCδ independently restored SRE-dependent transcription and immediate-early gene expression in senescent cells. Modulation of PKCδ activity in vivo with rottlerin or bistratene A altered senescent- and young-cell morphology, respectively. These observations support the idea that the coordinate transcriptional inhibition of several growth-associated genes by PKCδ contributes to the senescent phenotype.

Differential Regulation of Immediate Early Gene Expression in Preadipocyte Cells through Multiple Signaling Pathways

1999 ◽  
Vol 265 (3) ◽  
pp. 664-668 ◽  
Author(s):  
Hiroyuki Inuzuka ◽  
Rika Nanbu-Wakao ◽  
Yasuhiko Masuho ◽  
Masa-aki Muramatsu ◽  
Hideaki Tojo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Immediate Early Gene ◽  
Differential Regulation ◽  
Early Gene ◽  
Immediate Early ◽  
Early Gene Expression ◽  
Multiple Signaling

Induction of immediate early gene mRNAs and proteins by hCG in interstitial cells of rat testis

1995 ◽  
Vol 144 (3) ◽  
pp. 417-424 ◽  
Author(s):  
R Schultz ◽  
J Kononen ◽  
M Pelto-Huikko
Keyword(s):  
Transcriptional Response ◽  
Immediate Early Gene ◽  
Interstitial Cells ◽  
Early Gene ◽  
Immediate Early ◽  
Adaptive Responses ◽  
Rat Testis ◽  
Early Transcriptional Response

Abstract In the present study we have investigated the induction of immediate early gene (IEG) c-fos, c-jun, junB and junD mRNAs and proteins in interstitial cells of rat testis after hCG treatment in vivo using in situ hybridization and immunocytochemistry. The basal levels of all IEGs were barely detectable with our methods. A prominent induction of c-fos, c-jun and junB mRNAs and proteins in Leydig cells was seen after hCG treatment. The induction of these IEG mRNAs and proteins demonstrates that their expression is an early transcriptional response to the extracellular stimulus of hCG and that they are involved in transcriptional processes which may mediate the effects of LH on cellular adaptive responses or steroid biosynthesis. Journal of Endocrinology (1995) 144, 417–424

Phylogenetic relatedness and immediate early gene expression in black-capped chickadees

2012 ◽  
Author(s):  
Christopher B. Sturdy ◽  
Marc T. Avey ◽  
Laurie L. Bloomfield ◽  
Julie E. Elie ◽  
Todd M. Freeberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Phylogenetic Relatedness ◽  
Early Gene Expression
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