PMID- 30728766
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240214
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 12
DP  - 2019
TI  - Role for Chromatin Remodeling Factor Chd1 in Learning and Memory.
PG  - 3
LID - 10.3389/fnmol.2019.00003 [doi]
LID - 3
AB  - 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 Chd1 gene that gives rise to an N-terminally 
      truncated protein. Our data demonstrate that the Chd1 mutation negatively affects 
      long-term object recognition and short- and long-term spatial memory. We found 
      that Chd1 regulates hippocampal expression of the IEG early growth response 1 
      (Egr1) and activity-regulated cytoskeleton-associated (Arc) but not cFos and 
      brain derived neurotrophic factor (Bdnf), because the Chd1-mutation led to 
      dysregulation of Egr1 and Arc expression in naive mice and in mice analyzed at 
      different stages of object location memory (OLM) testing. Of note, Chd1 likely 
      regulates Egr1 in a direct manner, because chromatin immunoprecipitation (ChIP) 
      assays revealed enrichment of Chd1 upon stimulation at the Egr1 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.
FAU - Schoberleitner, Ines
AU  - Schoberleitner I
AD  - Division of Molecular Biology, Biocenter, Medical University of Innsbruck, 
      Innsbruck, Austria.
FAU - Mutti, Anna
AU  - Mutti A
AD  - Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Sah, Anupam
AU  - Sah A
AD  - Department of Pharmacology and Toxicology, Institute of Pharmacy and Centre for 
      Molecular Biosciences (CMBI), Leopold-Franzens University of Innsbruck, 
      Innsbruck, Austria.
FAU - Wille, Alexandra
AU  - Wille A
AD  - Division of Molecular Biology, Biocenter, Medical University of Innsbruck, 
      Innsbruck, Austria.
FAU - Gimeno-Valiente, Francisco
AU  - Gimeno-Valiente F
AD  - Institute of Health Research, INCLIVA, and Department of Biochemistry and 
      Molecular Biology, University of Valencia, Valencia, Spain.
FAU - Piatti, Paolo
AU  - Piatti P
AD  - Division of Molecular Biology, Biocenter, Medical University of Innsbruck, 
      Innsbruck, Austria.
FAU - Kharitonova, Maria
AU  - Kharitonova M
AD  - Department of Pharmacology and Toxicology, Institute of Pharmacy and Centre for 
      Molecular Biosciences (CMBI), Leopold-Franzens University of Innsbruck, 
      Innsbruck, Austria.
FAU - Torres, Luis
AU  - Torres L
AD  - Institute of Health Research, INCLIVA, and Department of Biochemistry and 
      Molecular Biology, University of Valencia, Valencia, Spain.
FAU - Lopez-Rodas, Gerardo
AU  - Lopez-Rodas G
AD  - Institute of Health Research, INCLIVA, and Department of Biochemistry and 
      Molecular Biology, University of Valencia, Valencia, Spain.
FAU - Liu, Jeffrey J
AU  - Liu JJ
AD  - Department of Proteomics and Signal Transduction, Max-Planck-Institute of 
      Biochemistry, Munich, Germany.
FAU - Singewald, Nicolas
AU  - Singewald N
AD  - Department of Pharmacology and Toxicology, Institute of Pharmacy and Centre for 
      Molecular Biosciences (CMBI), Leopold-Franzens University of Innsbruck, 
      Innsbruck, Austria.
FAU - Schwarzer, Christoph
AU  - Schwarzer C
AD  - Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Lusser, Alexandra
AU  - Lusser A
AD  - Division of Molecular Biology, Biocenter, Medical University of Innsbruck, 
      Innsbruck, Austria.
LA  - eng
GR  - P 31377/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
DEP - 20190123
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC6351481
OTO - NOTNLM
OT  - chromatin
OT  - cognition
OT  - epigenetics
OT  - gene expression
OT  - hippocampus
OT  - immediate early genes
OT  - learning
OT  - memory
EDAT- 2019/02/08 06:00
MHDA- 2019/02/08 06:01
PMCR- 2019/01/01
CRDT- 2019/02/08 06:00
PHST- 2018/09/03 00:00 [received]
PHST- 2019/01/08 00:00 [accepted]
PHST- 2019/02/08 06:00 [entrez]
PHST- 2019/02/08 06:00 [pubmed]
PHST- 2019/02/08 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2019.00003 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2019 Jan 23;12:3. doi: 10.3389/fnmol.2019.00003. eCollection 
      2019.