Coactivator

Coactivator

A coactivator is a type of protein that increases the rate of gene expression by binding to an activator (or transcription factor) which contains a DNA-binding domain. Coactivators are essential components of the transcriptional regulation machinery in eukaryotic cells. They do not directly bind to DNA but instead interact with transcription factors to enhance the transcription of specific genes.

Function

Coactivators function by modifying the structure of chromatin or by recruiting the RNA polymerase complex to the promoter region of a gene. They often possess histone acetyltransferase (HAT) activity, which acetylates histone proteins, leading to a more open chromatin structure and increased accessibility of the DNA to transcription factors and the transcriptional machinery.

Mechanism of Action

Coactivators can be classified based on their mechanism of action:

• Chromatin Remodeling: Coactivators such as CBP/p300 have HAT activity that modifies histones, leading to chromatin relaxation.
• Mediator Complex: The Mediator complex acts as a bridge between transcription factors and the RNA polymerase II complex, facilitating transcription initiation.
• Recruitment of General Transcription Factors: Coactivators can recruit general transcription factors to the promoter region, enhancing the assembly of the transcriptional machinery.

Examples

Some well-known coactivators include:

• CBP/p300: These are transcriptional coactivators with intrinsic HAT activity, involved in the regulation of genes controlling cell growth and division.
• SRC-1: Steroid receptor coactivator-1, which interacts with nuclear hormone receptors to enhance transcription.
• Mediator: A multi-subunit complex that serves as a coactivator for RNA polymerase II-dependent transcription.

Clinical Significance

Dysregulation of coactivator function can lead to various diseases, including cancer. For example, overexpression of CBP/p300 has been associated with certain types of cancer due to its role in promoting cell proliferation.

Research and Development

Research into coactivators is ongoing, with studies focusing on their role in gene regulation, their interaction with transcription factors, and their potential as targets for therapeutic intervention in diseases such as cancer and metabolic disorders.

See Also

• Corepressor
• Transcription factor
• Gene expression

External Links

• National Center for Biotechnology Information
• National Human Genome Research Institute