A transactivation domain (TAD) is a region within a transcription factor that is responsible for activating gene transcription. It does this by interacting with other proteins — such as coactivators or the transcriptional machinery — to initiate or enhance the expression of specific target genes.
🔑 Definition:
A transactivation domain is a functional part of a transcription factor that helps recruit and activate RNA polymerase II and associated proteins, enabling the transcription of DNA into messenger RNA (mRNA).
⚙️ What It Does:
When a transcription factor binds to a specific DNA sequence (usually in the promoter region of a gene), the transactivation domain:
- Recruits coactivator proteins (e.g., CBP/p300, Mediator complex)
- Attracts chromatin modifiers (like histone acetyltransferases)
- Stabilizes the transcription initiation complex, helping RNA polymerase II start transcription
- Enhances the rate or strength of gene expression
📍 Where Is It Found?
Transactivation domains are one part of a transcription factor. A typical transcription factor has:
| Domain | Function |
|---|---|
| DNA-binding domain (DBD) | Binds to specific DNA sequences |
| Transactivation domain (TAD) | Recruits and activates transcription machinery |
| Regulatory domains | Respond to signals, modify activity |
🧪 Example: p65 in the NF-κB Pathway
- The p65 subunit of NF-κB contains a strong transactivation domain.
- When the p65/p50 dimer enters the nucleus, only p65 has the ability to turn on genes because p50 lacks a TAD.
- That’s why p65 is essential for activating inflammatory and immune genes.
🧠 Why It Matters:
| Relevance | Impact |
|---|---|
| Gene expression control | TADs are crucial for turning genes “on” |
| Disease research | Mutations in TADs can lead to cancers or developmental disorders |
| Drug development | Blocking or mimicking TADs can regulate overactive genes (e.g., in cancer or autoimmunity) |
📌 Summary:
A transactivation domain (TAD) is the part of a transcription factor that activates gene expression by attracting the cell’s transcription machinery. Without it, the transcription factor might bind DNA but would be unable to “turn on” the gene.