Role for Chromatin Remodeling Factor Chd1 in Learning and Memory

• Published in: Frontiers in molecular neuroscience Vol. 12; p. 3
• Main Authors: Schoberleitner, Ines, Mutti, Anna, Sah, Anupam, Wille, Alexandra, Gimeno-Valiente, Francisco, Piatti, Paolo, Kharitonova, Maria, Torres, Luis, López-Rodas, Gerardo, Liu, Jeffrey J, Singewald, Nicolas, Schwarzer, Christoph, Lusser, Alexandra
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 23.01.2019; Frontiers Media S.A
• Subjects: Biochemistry; Brain-derived neurotrophic factor; chromatin; Chromatin remodeling; cognition; Cognition & reasoning; Cognitive ability; Deoxyribonucleic acid; DNA; DNA methylation; EGR-1 protein; Epigenetics; Gene expression; Gene regulation; Hippocampus; Histones; immediate early genes; Immediate-early proteins; learning; Long term memory; Memory; Molecular biology; Molecular modelling; Mutation; Neuroscience; Pattern recognition; Proteins; Serine; Signal transduction; Spatial memory; Stem cells; Austria; Germany; memory; cognition; hippocampus; immediate early genes; learning; chromatin; epigenetics; gene expression
• ISSN: 1662-5099; 1662-5099
• DOI: 10.3389/fnmol.2019.00003

Precise temporal and spatial regulation of gene expression in the brain is a prerequisite for cognitive processes such as learning and memory. Epigenetic mechanisms that modulate the chromatin structure have emerged as important regulators in this context. While posttranslational modification of histones or the modification of DNA bases have been examined in detail in many studies, the role of ATP-dependent chromatin remodeling factors (ChRFs) in learning- and memory-associated gene regulation has largely remained obscure. Here we present data that implicate the highly conserved chromatin assembly and remodeling factor Chd1 in memory formation and the control of immediate early gene (IEG) response in the hippocampus. We used various paradigms to assess short-and long-term memory in mice bearing a mutated gene that gives rise to an N-terminally truncated protein. Our data demonstrate that the mutation negatively affects long-term object recognition and short- and long-term spatial memory. We found that Chd1 regulates hippocampal expression of the IEG ( ) and ( ) but not and ( ), because the -mutation led to dysregulation of and expression in naive mice and in mice analyzed at different stages of object location memory (OLM) testing. Of note, Chd1 likely regulates in a direct manner, because chromatin immunoprecipitation (ChIP) assays revealed enrichment of Chd1 upon stimulation at the genomic locus in the hippocampus and in cultured cells. Together these data support a role for Chd1 as a critical regulator of molecular mechanisms governing memory-related processes, and they show that this function involves the N-terminal serine-rich region of the protein.