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11:31
Single-molecule Imaging of Gene Regulation In vivo Using Cotranslational Activation by Cleavage (CoTrAC)
Published on: March 15, 2013
A transcriptional switch mediated by cofactor methylation
1Gene Expression Laboratory, Department of Biological Chemistry, University of California Davis Cancer Center/Basic Science, Sacramento, CA 95817, USA.
Science (New York, N.Y.)
|November 10, 2001
Summary
Controlled methylation of proteins like CREB-binding proteins (CBP)/p300 acts as a molecular switch. This cofactor methylation regulates gene activation in hormone signaling pathways.
Area of Science:
- Molecular Biology
- Epigenetics
- Gene Regulation
Background:
- Transcriptional cofactors CREB-binding proteins (CBP)/p300 play crucial roles in gene activation.
- These cofactors possess a KIX domain essential for recruiting transcription factors like CREB.
- Post-translational modifications, such as methylation, are increasingly recognized as key regulatory mechanisms.
Purpose of the Study:
- To investigate the role of methylation in regulating the function of CBP/p300.
- To elucidate the mechanism by which coactivator-associated arginine methyltransferase 1 (CARM1) affects CREB activation.
- To define cofactor methylation as a novel regulatory mechanism in hormone signaling.
Main Methods:
- In vivo and in vitro experiments were conducted.
- Site-directed mutagenesis was used to identify the methylation site on CBP/p300.
- Assays were performed to assess the interaction between CBP/p300 and CREB, and the effect of CARM1-mediated methylation.
Main Results:
- A specific arginine residue on the KIX domain of CBP/p300 was identified as a methylation site.
- Methylation of this site by CARM1 inhibits the interaction between the KIX domain and the kinase inducible domain (KID) of CREB.
- CARM1 functions as a repressor in cyclic adenosine monophosphate (cAMP) signaling but as an activator for nuclear hormone signaling.
Conclusions:
- Cofactor methylation, specifically by CARM1, acts as a molecular switch controlling gene transcription.
- Histone methylation plays a significant role in hormone-induced gene activation.
- Cofactor methylation represents a newly identified regulatory mechanism within hormone signaling pathways.
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