| Title | Protein phosphatase 1 regulates the histone code for long-term memory. | | Author(s) | Koshibu K, Gräff J, Beullens M, Heitz FD, Berchtold D, Russig H, Farinelli M, Bollen M, Mansuy IM | | Institution | Brain Research Institute, University of Zürich, Swiss Federal Institute of Technology, CH-8057 Zurich, Switzerland. | | Source | J Neurosci 2009 Oct 14; 29(41):13079-89. | | MeSH | Analysis of Variance
Animals
Calcium-Calmodulin-Dependent Protein Kinase Kinase
Cell Nucleus
Chromatin Assembly and Disassembly
Chromatin Immunoprecipitation
Discrimination Learning
Doxycycline
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation
Green Fluorescent Proteins
Hippocampus
Histone Code
Histone Deacetylases
Histones
Memory
Mice
Mice, Transgenic
Neurons
Neuropsychological Tests
Oxidoreductases, N-Demethylating
Prosencephalon
Protein Phosphatase 1
Transduction, Genetic
| | Abstract | Chromatin remodeling through histone posttranslational modifications (PTMs) and DNA methylation has recently been implicated in cognitive functions, but the mechanisms involved in such epigenetic regulation remain poorly understood. Here, we show that protein phosphatase 1 (PP1) is a critical regulator of chromatin remodeling in the mammalian brain that controls histone PTMs and gene transcription associated with long-term memory. Our data show that PP1 is present at the chromatin in brain cells and interacts with enzymes of the epigenetic machinery including HDAC1 (histone deacetylase 1) and histone demethylase JMJD2A (jumonji domain-containing protein 2A). The selective inhibition of the nuclear pool of PP1 in forebrain neurons in transgenic mice is shown to induce several histone PTMs that include not only phosphorylation but also acetylation and methylation. These PTMs are residue-specific and occur at the promoter of genes important for memory formation like CREB (cAMP response element-binding protein) and NF-kappaB (nuclear factor-kappaB). These histone PTMs further co-occur with selective binding of RNA polymerase II and altered gene transcription, and are associated with improved long-term memory for objects and space. Together, these findings reveal a novel mechanism for the epigenetic control of gene transcription and long-term memory in the adult brain that depends on PP1. | | Language | eng | | Pub Type(s) | In Vitro
Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19828821 |
|
