A transcriptional switch mediated by cofactor methylation

W. Xu, H. Chen, K. Du, H. Asahara, M. Tini, Beverly Emerson, M. Montminy, R. H. Evans

Research output: Contribution to journalArticle

313 Citations (Scopus)

Abstract

We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.

Original languageEnglish (US)
Pages (from-to)2507-2511
Number of pages5
JournalScience
Volume294
Issue number5551
DOIs
StatePublished - Dec 21 2001
Externally publishedYes

Fingerprint

Methylation
CREB-Binding Protein
Hormones
Co-Repressor Proteins
Nucleosomes
Methyltransferases
Cyclic AMP
Histones
Transcriptional Activation
Arginine
Phosphotransferases
coactivator-associated arginine methyltransferase 1

ASJC Scopus subject areas

  • General

Cite this

Xu, W., Chen, H., Du, K., Asahara, H., Tini, M., Emerson, B., ... Evans, R. H. (2001). A transcriptional switch mediated by cofactor methylation. Science, 294(5551), 2507-2511. https://doi.org/10.1126/science.1065961

A transcriptional switch mediated by cofactor methylation. / Xu, W.; Chen, H.; Du, K.; Asahara, H.; Tini, M.; Emerson, Beverly; Montminy, M.; Evans, R. H.

In: Science, Vol. 294, No. 5551, 21.12.2001, p. 2507-2511.

Research output: Contribution to journalArticle

Xu, W, Chen, H, Du, K, Asahara, H, Tini, M, Emerson, B, Montminy, M & Evans, RH 2001, 'A transcriptional switch mediated by cofactor methylation', Science, vol. 294, no. 5551, pp. 2507-2511. https://doi.org/10.1126/science.1065961
Xu W, Chen H, Du K, Asahara H, Tini M, Emerson B et al. A transcriptional switch mediated by cofactor methylation. Science. 2001 Dec 21;294(5551):2507-2511. https://doi.org/10.1126/science.1065961
Xu, W. ; Chen, H. ; Du, K. ; Asahara, H. ; Tini, M. ; Emerson, Beverly ; Montminy, M. ; Evans, R. H. / A transcriptional switch mediated by cofactor methylation. In: Science. 2001 ; Vol. 294, No. 5551. pp. 2507-2511.
@article{f8f1ea5bb88d4a16b3aa36579a39f004,
title = "A transcriptional switch mediated by cofactor methylation",
abstract = "We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.",
author = "W. Xu and H. Chen and K. Du and H. Asahara and M. Tini and Beverly Emerson and M. Montminy and Evans, {R. H.}",
year = "2001",
month = "12",
day = "21",
doi = "10.1126/science.1065961",
language = "English (US)",
volume = "294",
pages = "2507--2511",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5551",

}

TY - JOUR

T1 - A transcriptional switch mediated by cofactor methylation

AU - Xu, W.

AU - Chen, H.

AU - Du, K.

AU - Asahara, H.

AU - Tini, M.

AU - Emerson, Beverly

AU - Montminy, M.

AU - Evans, R. H.

PY - 2001/12/21

Y1 - 2001/12/21

N2 - We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.

AB - We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.

UR - http://www.scopus.com/inward/record.url?scp=0035930726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035930726&partnerID=8YFLogxK

U2 - 10.1126/science.1065961

DO - 10.1126/science.1065961

M3 - Article

VL - 294

SP - 2507

EP - 2511

JO - Science

JF - Science

SN - 0036-8075

IS - 5551

ER -