The CBP co-activator is a histone acetyltransferase

Area of Science:

• Molecular Biology
• Epigenetics
• Gene Regulation

Background:

• CREB-binding protein (CBP) functions as a transcriptional adaptor, facilitating interactions between DNA-bound activators and the transcription machinery.
• CBP is known to recruit the histone acetyltransferase (HAT) P/CAF, a process thought to contribute to transcriptional stimulation.

Purpose of the Study:

• To investigate the intrinsic enzymatic activity of the CBP protein.
• To determine if CBP possesses its own histone acetyltransferase (HAT) activity.
• To elucidate the role of the transcriptional activator E1A in modulating CBP's HAT activity.

Main Methods:

• Biochemical assays to assess the HAT activity of purified CBP protein.
• Analysis of the interaction between CBP, P/CAF, and E1A using co-immunoprecipitation or similar techniques.
• Characterization of the HAT domain's location within CBP relative to the E1A binding site.

Main Results:

• CBP exhibits intrinsic histone acetyltransferase (HAT) activity.
• The HAT domain of CBP is located adjacent to the E1A binding site.
• The transcriptional activator E1A displaces P/CAF from CBP but does not inhibit CBP's associated HAT activity.
• E1A effectively carries CBP's HAT activity when bound to it.

Conclusions:

• CBP possesses intrinsic HAT activity, distinct from its ability to recruit other HATs like P/CAF.
• The transcriptional activator E1A can associate with CBP and utilize its intrinsic HAT activity.
• Targeting CBP-associated HAT activity to specific promoters via E1A is a potential mechanism for E1A-mediated transcriptional activation.