The transcription factor TFIID complex contains TATA-Box Binding Protein Associated Factor 9B (TAF9B) which functions in the regulation of gene transcription by RNA polymerase II. Recent research shows that TAF9B has a significant impact on neuronal gene expression regulation throughout neurodevelopment and neuroplasticity. The transcription initiation complex TFIID contains TAF9B as a component and experiences increased expression during neuronal differentiation to regulate neurodevelopment and neuroplasticity.
Fig 1. TAF9B is upregulated during neuronal differentiation (Herrera, F., et al. 2014).
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Role of TAF9B in Neuronal Gene Expression
Promoting Neuron-specific Gene Expression
The TFIID complex contains TAF9B which alters RNA Pol II-based transcription initiation and controls specific gene expression in neurons. Research demonstrates that TAF9B loss results in reduced expression of neuron-specific genes which disrupts both neuronal growth and function.
Affecting Neuroplasticity
TAF9B likely influences synaptic plasticity through the regulation of neural activity-related genes including ARC and BDNF. The process of learning and memory depends on this function but it is also linked to neurological conditions like Alzheimer's disease and autism.
Regulating CREB-related Transcriptional Programs
TAF9B enhances neuronal survival and synapse formation through its ability to increase CREB-based transcription activity. The CREB protein serves as a key controller of neuronal plasticity while also influencing long-term potentiation processes.
Role in Neural Stem Cell Differentiation
Research findings demonstrate TAF9B as an essential element in the conversion of neural stem cells into mature neurons. TAF9B functions as a promoter for neuronal fate determination through its regulatory effects on transcription factor networks including NEUROD1 and ASCL1.
TAF9B-related Neurological Diseases
| Neurodevelopmental disorders |
Alterations in TAF9B expression can produce neuronal differentiation defects that correlate with autism spectrum disorder (ASD). |
| Psychiatric disorders |
TAF9B may play a role in Alzheimer's disease and Parkinson's disease pathologies through its effects on synaptic activity and gene transcription. |
TAF9B Upregulated During Neuronal Differentiation
Neural stem cell differentiation into neurons triggers an increase in TAF9B expression. Research demonstrates that TAF9B expression levels become significantly elevated when neural stem cells differentiate into mature neurons. The temporal increase in TAF9B levels indicates its potential role as a central controller in determining neuronal fate and activating genes.
- Undifferentiated stage: TAF9B expression is low and neural stem cells are in a proliferative state.
- Early differentiation stage: TAF9B begins to be upregulated, promoting the transcription of neuron-specific genes.
- Mature neuron stage: TAF9B maintains a high level to support neuronal function and plasticity.
TAF9B Promotes Neuron-specific Gene Expression
Activates neuron-specific transcription factors
TAF9B promotes the expression of neuron-related genes by enhancing RNA Pol II-dependent transcription, such as:
- NEUROD1 (neuronal differentiation factor)
- ASCL1 (promotes neuronal fate determination)
- TBR1 (regulates cortical neuron development)
- Affects CREB-dependent gene regulation
TAF9B may promote promotes neuronal survival and synaptic plasticity. EGR1 regulates neuronal plasticity and learning and memory by interacting with CREB (cAMP Response Element-Binding Protein).
TAF9B as A Potential Therapeutic Target
- Gene therapy: Regulate TAF9B expression through gene editing or CRISPR technology to restore neuronal function.
- Small molecule agonists/inhibitors: Design TAF9B-related transcriptional regulators as drugs to improve neuronal survival.
- Neuroplasticity enhancement therapy: Promote synapse formation through environmental stimulation (cognitive training, exercise) combined with TAF9B-related pathways.
TAF9B-mediated Epigenetic Regulation of Neuronal Gene Expression
The expression of neuronal genes gets promoted by TAF9B through chromatin state changes characterized by H3K27ac that enable a more open chromatin configuration. The activation of genes related to neurons requires the recruitment of CBP/p300 acetyltransferase. Epigenetic changes account for the dynamic activation process of TAF9B throughout neuronal development.
TAF9B is upregulated during neuronal differentiation. Within the transcription factor TFIID complex TAF9B serves as a vital component for regulating neuronal gene expression while also influencing neural plasticity and neurological diseases. A deeper investigation into how TAF9B operates could lead to innovative treatments for neurodevelopmental and neurodegenerative conditions.
References
- Herrera, F., et al. Core promoter factor TAF9B regulates neuronal gene expression. Elife. 2014, 3: e02559.
- Frontini, M., et al. TAF9b (formerly TAF9L) is a bona fide TAF that has unique and overlapping roles with TAF9. Molecular and cellular biology. 2005, 25(11): 4638-4649.
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