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Related Experiment Video

Updated: Jul 17, 2026

Single-molecule Imaging of Gene Regulation In vivo Using Cotranslational Activation by Cleavage (CoTrAC)

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.

W Xu¹, H Chen, K Du

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.

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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

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Published on: September 20, 2018

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.