Faculty Collaboration Database

Acetylation curtails nucleosome binding, not stable nucleosome remodeling, by FoxO1. Biochem Biophys Res Commun 2009 Feb 20;379(4):1005-8

Date

01/17/2009

Pubmed ID

19146829

DOI

10.1016/j.bbrc.2009.01.014

Scopus ID

2-s2.0-58949091250 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

Transcriptional activity of FoxO factors is controlled through the actions of multiple growth factors signaling through protein kinase B, whereby phosphorylation of FoxO factors inhibits FoxO-mediated transactivation by promoting nuclear export. Phosphorylation of FoxO factors is enhanced by p300-mediated acetylation, which decreases their affinity for DNA. The negative effect of acetylation on FoxO DNA binding, together with nuclear FoxO mobility, is eliminated by over-expression of the de-acetylase Sirt1, suggesting that acetylation mobilizes FoxO factors in chromatin for inducible gene expression. Here, we show that acetylation significantly curtails the affinity of FoxO1 for its binding sites in nucleosomal DNA but has no effect on either stable nucleosome binding or remodeling by this factor. We suggest that, while acetylation provides a first, essential step toward mobilizing FoxO factors for inducible gene repression, additional mechanisms exist for overcoming their inherent capacity to stably bind and remodel nuclear chromatin.

Author List

Hatta M, Liu F, Cirillo LA

Author

Lisa A. Cirillo PhD Assistant Dean, Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylation
Amino Acid Substitution
Animals
Binding Sites
DNA
Forkhead Box Protein O1
Forkhead Transcription Factors
Lysine
Mice
Nucleosomes