PMID- 30067287
OWN - NLM
STAT- MEDLINE
DCOM- 20190826
LR  - 20211204
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Linking)
VI  - 28
IP  - 11
DP  - 2018 Nov
TI  - Global epigenetic analysis of BDNF Val66Met mice hippocampus reveals changes in 
      dendrite and spine remodeling genes.
PG  - 783-795
LID - 10.1002/hipo.22991 [doi]
AB  - Brain-derived neurotrophic factor (BDNF), a neurotrophin highly expressed in the 
      hippocampus, plays crucial roles in cognition, neuroplasticity, synaptic 
      function, and dendritic remodeling. The common human Val66Met polymorphism of 
      BDNF has been implicated in the pathophysiology of neuropsychiatric and 
      neurodegenerative disorders, and in the outcome of pro-adaptive and therapeutic 
      treatments. Altered gene-expression profile has been previously shown in BDNF 
      Val66Met knock-in mice, which recapitulate the phenotypic hallmarks of 
      individuals carrying the BDNF Met allele. The aim of this study was to 
      investigate the impact of the BDNF Val66Met polymorphism in the knock-in mouse 
      model on two hippocampal epigenetic marks for transcriptional repression and 
      activation, respectively: trimethylation of lysine 27 on histone H3 (H3K27me3) 
      and acetylation of histone H3 (AcH3), using a genome-wide approach. Chromatin 
      immunoprecipitation followed by deep sequencing of immunoprecipitated DNA 
      (ChIP-Seq) was carried out with specific antibodies for H3K27me3 and AcH3. Our 
      results revealed broad alteration of H3K27me3 and AcH3 marks association profiles 
      in BDNF(Met/Met) , compared to BDNF(Val/Val) mice. Bioinformatics analysis showed 
      changes in several biological functions and related pathways, affected by the 
      presence of the polymorphism. In particular, a number of networks of functional 
      interaction contained BDNF as central node. Quantitative PCR analysis confirmed 
      epigenetically related significant changes in the expression of five genes: Dvl1, 
      Nos3, Reln, Lypd6, and Sh3gl2. The first three are involved in dendrite and spine 
      remodeling, morphological features altered in BDNF(Met/Met) mice. This work in 
      homozygous knock-in mice shows that the human BDNF Val66Met polymorphism induces 
      an array of histone H3 epigenetic modifications, in turn altering the expression 
      of select genes crucial for structural and functional neuronal features.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Mallei, Alessandra
AU  - Mallei A
AD  - Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento 
      di Scienze Farmacologiche e Biomolecolari and CEND, Universita degli Studi di 
      Milano, Milan, Italy.
FAU - Ieraci, Alessandro
AU  - Ieraci A
AD  - Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento 
      di Scienze Farmacologiche e Biomolecolari and CEND, Universita degli Studi di 
      Milano, Milan, Italy.
FAU - Corna, Stefano
AU  - Corna S
AD  - Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento 
      di Scienze Farmacologiche e Biomolecolari and CEND, Universita degli Studi di 
      Milano, Milan, Italy.
FAU - Tardito, Daniela
AU  - Tardito D
AD  - Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento 
      di Scienze Farmacologiche e Biomolecolari and CEND, Universita degli Studi di 
      Milano, Milan, Italy.
FAU - Lee, Francis S
AU  - Lee FS
AD  - Department of Psychiatry, Weill Cornell Medical College of Cornell University, 
      New York, New York.
FAU - Popoli, Maurizio
AU  - Popoli M
AUID- ORCID: 0000-0003-4670-8664
AD  - Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento 
      di Scienze Farmacologiche e Biomolecolari and CEND, Universita degli Studi di 
      Milano, Milan, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (Histones)
RN  - 0 (Reelin Protein)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 3.4.21.- (RELN protein, human)
RN  - EC 3.4.21.- (Reln protein, mouse)
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/*metabolism
MH  - Computational Biology
MH  - Dendrites/*metabolism
MH  - *Epigenesis, Genetic
MH  - Gene Knock-In Techniques
MH  - Hippocampus/*metabolism
MH  - Histones/genetics/metabolism
MH  - Humans
MH  - Male
MH  - Mice, Transgenic
MH  - *Polymorphism, Genetic
MH  - Reelin Protein
MH  - Wnt Proteins/metabolism
MH  - beta Catenin/metabolism
OTO - NOTNLM
OT  - BDNF polymorphism
OT  - ChIP-Seq
OT  - epigenetics
OT  - gene expression
OT  - synaptic remodeling
EDAT- 2018/08/02 06:00
MHDA- 2019/08/27 06:00
CRDT- 2018/08/02 06:00
PHST- 2018/01/16 00:00 [received]
PHST- 2018/05/15 00:00 [revised]
PHST- 2018/05/24 00:00 [accepted]
PHST- 2018/08/02 06:00 [pubmed]
PHST- 2019/08/27 06:00 [medline]
PHST- 2018/08/02 06:00 [entrez]
AID - 10.1002/hipo.22991 [doi]
PST - ppublish
SO  - Hippocampus. 2018 Nov;28(11):783-795. doi: 10.1002/hipo.22991.