Chromatin opening and stable perturbation of core histone:DNA contacts by FoxO1. J Biol Chem 2007 Dec 07;282(49):35583-93
Date
10/10/2007Pubmed ID
17923482DOI
10.1074/jbc.M704735200Scopus ID
2-s2.0-37249054901 (requires institutional sign-in at Scopus site) 103 CitationsAbstract
FoxO1, a member of the forkhead rabdomyosarcoma (FoxO) subfamily of transcription factors, binds DNA via a highly conserved winged-helix "forkhead box" motif used by other regulatory proteins to mediate their effects through chromatin binding and remodeling. To examine how FoxO1 regulates target genes in chromatin, we studied the binding of purified recombinant FoxO1 protein to nucleosome particles and chromatin arrays containing the insulin-like growth factor-binding protein 1 promoter. We found that FoxO1 is able to bind to its cognate sites within the insulin-like growth factor-binding protein 1 promoter on a nucleosome. This binding stably perturbs core histone:DNA contacts extending up- and downstream from sites of FoxO1 binding without disrupting the underlying core particle. FoxO1 is able to harness these capabilities to bind to and de-condense linker histone-compacted chromatin arrays. Chromatin opening by FoxO1 requires both the N and C termini of the protein, which are also required for high affinity core histone binding and, in the case of the N terminus, nucleosome perturbation. We suggest that the chromatin binding and remodeling functions revealed here for FoxO1 endow all FoxO factors with the ability to initiate and dynamically modulate active chromatin states, enabling their diverse roles as gene regulatory factors in metabolism, cell survival, apoptosis, cell cycle progression, DNA repair, and protection against oxidative stress.
Author List
Hatta M, Cirillo LAAuthor
Lisa A. Cirillo PhD Assistant Dean, Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Cell Cycle
Cell Survival
Cell-Free System
Chromatin Assembly and Disassembly
DNA
DNA Repair
Forkhead Box Protein O1
Forkhead Transcription Factors
Histones
Insulin-Like Growth Factor Binding Protein 1
Mice
Nucleosomes
Oxidative Stress
Promoter Regions, Genetic
Protein Binding
Rats
Recombinant Proteins
Xenopus laevis
