Elsevier

Advances in Biological Regulation

Volume 62, September 2016, Pages 37-49
Advances in Biological Regulation

Gene regulation in the immediate-early response process

https://doi.org/10.1016/j.jbior.2016.05.001Get rights and content
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Abstract

Immediate-early genes (IEGs) can be activated and transcribed within minutes after stimulation, without the need for de novo protein synthesis, and they are stimulated in response to both cell-extrinsic and cell-intrinsic signals. Extracellular signals are transduced from the cell surface, through receptors activating a chain of proteins in the cell, in particular extracellular-signal-regulated kinases (ERKs), mitogen-activated protein kinases (MAPKs) and members of the RhoA-actin pathway. These communicate through a signaling cascade by adding phosphate groups to neighboring proteins, and this will eventually activate and translocate TFs to the nucleus and thereby induce gene expression. The gene activation also involves proximal and distal enhancers that interact with promoters to simulate gene expression. The immediate-early genes have essential biological roles, in particular in stress response, like the immune system, and in differentiation. Therefore they also have important roles in various diseases, including cancer development. In this paper we summarize some recent advances on key aspects of the activation and regulation of immediate-early genes.

Keywords

Immediate-early response
Signaling cascades
Poised genes
Transcription factors
Enhancers

Abbreviations

IER
immediate-early response
IEG
immediate-early gene
PRG
primary response gene
SRG
secondary response genes
PDGF
platelet-derived growth factor
EGF
epidermal growth factor
SRF
serum-response factor
NF-kB
nuclear factor-kB
CREB
cyclic AMP response element-binding protein
AP-1
activator protein-1
TCF
ternary complex factor
ERK
extracellular signal-regulated kinase
MAPK
Mitogen-activated protein kinases
ELK1
E26-like kinase
MRTF
myocardin related transcription factor
NF1
nuclear factor 1
PARP1
Poly (ADP-ribose) polymerase 1
RSK
p90 ribosomal S6 kinase
JNK
c-Jun N- terminal kinase
ERK5
extracellular signal regulated kinase-5
BMK1
Big MAP kinase-1
MSK
Mitogen/stress activated protein kinase
RNA Pol II
RNA polymerase II
GO
Gene Ontology
TBP
TATA binding protein
TSS
Transcription Start Site
HAT
histone acetyl transferase
IRF3
interferon regulatory factor 3
TLR
Toll-like receptor
NGF
nerve growth factor
G protein
guanine nucleotide binding protein
TF
Transcription Factor
MKL
megakaryoblastic leukemia
ESC
embryonic stem cells
DSIF
DRB sensitivity-inducing factor
NELF
negative elongation factor
P-TEFb
positive transcription elongation factor
CTD
C-terminal domain
eRNA
enhancer RNA

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