Medical College of Wisconsin
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Stable chromatin binding prevents FoxA acetylation, preserving FoxA chromatin remodeling. J Biol Chem 2010 Jan 01;285(1):464-72

Date

11/10/2009

Pubmed ID

19897491

Pubmed Central ID

PMC2804194

DOI

10.1074/jbc.M109.063149

Scopus ID

2-s2.0-73649108251   23 Citations

Abstract

FoxA1-3 (formerly HNF3alpha, -beta, and -gamma), members of the FoxA subfamily of forkhead transcription factors, function as initial chromatin-binding and chromatin-remodeling factors in a variety of tissues, including liver and pancreas. Despite essential roles in development and metabolism, regulation of FoxA factors is not well understood. This study examines a potential role for acetylation in the regulation of FoxA chromatin binding and remodeling. Using in silico analysis, we have identified 11 putative p300 acetylation sites within FoxA1, five of which are located within wings 1 and 2 of its winged-helix DNA-binding domain. These polypeptide structures stabilize FoxA DNA and chromatin binding, and we have demonstrated that acetylation attenuates FoxA binding to DNA and diminishes its ability to remodel chromatin. FoxA acetylation is inhibited by chromatin binding. We propose a model whereby stable chromatin binding protects the FoxA DNA-binding domain from acetylation to preserve chromatin binding and remodeling by FoxA factors in the absence of extracellular cues.

Author List

Kohler S, 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
Animals
Chromatin
Chromatin Assembly and Disassembly
DNA
Enhancer Elements, Genetic
Hep G2 Cells
Hepatocyte Nuclear Factor 3-alpha
Hepatocytes
Humans
Mice
Nucleosomes
Protein Binding
p300-CBP Transcription Factors