BIO254:Transcription
Introduction
In activity-dependent transcription, a postsynaptic neuron changes its transcription of specific genes in response to synaptic activity. Both long-term and short-term changes are produced by synaptic activity. Long-term changes, such as synaptic plasticity and neuronal development, are often caused by changes in gene expression.
General Mechanism for Activity-Dependent Transcription
Following are the steps between the neuronal activity and the changes in gene expression:
A) Neuronal Activity
The presynaptic neuron excites or inhibits the postsynaptic neuron using neurotransmitters, such as glutamate or GABA.
B) Postsynaptic Response
The neurotransmitter activates metabotropic and/or ionotropic receptors activating G-protein/second messenger systems or producing ionic currents, respectively.
C) Signaling Pathways
Signaling proteins are activated (phosporylated/dephosphorylated) by either the G-protein pathways or the pathways affected by ionic concentrations (usually Ca2+ dependent). These pathways are often referred to as cascades because of the multiple proteins phosphorylated/dephosphorylated sequentially in a pathway.
D) Nuclear Localization
An activated protein enters the nucleus and activates/inactivates an activating or repressing transcription factor. In some cases, the protein that enters the nucleus is itself an activated transcription factor which goes directly and binds to its specific DNA sequence.
E) Transcription Factor Binding/Unbinding to DNA
The transcription factor then binds to or breaks away from the DNA, depending on whether the transcription factor was activated or inactivated, respectively.
Transcription Factors
Along with protein-coding regions, the gene's DNA includes sequences that are involved in the control of the gene's expression. These sequences are called regulatory elements; transcription factors are sequence specific and bind to regulatory elements containing its binding sequence. For example, CREB binds to the DNA sequence CRE (cAMP response element). In eukaryotes, the transcription of DNA to mRNA is carried out by RNA Polymerase II, which binds to the gene's promoter region. Transcription factors affect the ability of the polymerase to bind to the promoter region, thereby influencing the level of expression of the gene.
F) Gene expression Increased/Decreased
Depending on whether the transcription factor is activated or inactivated and whether the transcription factor itself activates or represses gene expression, the transcription of the target gene(s) will be changed.
How Gene Expression is Changed
Examples of Pathways that Affect Transcription
Activation of CREB
Images of CREB Pathway:
UT Houston Simple picture of neurotransmitter activation of G-protein, increase of cAMP concentration, activation of PKA, and activation of CREB
Humboldt University, Berlin Simple picture of pathway from Ca2+ increase to CREB activation
Panomics Simple picture of various pathways influencing CREB
Eurekah Small picture that shows effect of neurotransmitter, Ca2+ increase, and growth factors on CREB
Sigma Aldrich CREB activation by growth factors
Biocarta Complicated picture of various pathways influencing CREB
Protein Abbreviations
CREB: cAMP responsive element binding protein
CBP: CREB binding protein
ROS: reactive oxygen species
PKA: protein kinase A
ERK: extracellular regulated kinase
MEK: MAPK kinase
PI3-K: phopshatidyl inositol3 kinase
GSK3: glycogen synthase kinase 3B
CaM: calmodulin
Ca2+/CaM: calcium calmodulin (calcium bound to calmodulin)
CaMKK: calmodulin kinase kinase
CaMKIV:
CRE: CREB response element
History
Notes
This article has focused on activity-dependent transcription in neurons. Activity-dependent transcription occurs in various excitable cells, such as muscle cells (ie, Wamhoff et. al. 2006).
References
Wamhoff BR, Bowles DK, Owens GK. Excitation-transcription coupling in arterial smooth muscle. Circ Res. 2006 Apr 14;98(7):868-78.
Squire LR, et al. Fundamental Neuroscience. Academic Press, Boston, 2003.
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