PMID- 26842245
OWN - NLM
STAT- MEDLINE
DCOM- 20161027
LR  - 20181113
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 40
IP  - 2
DP  - 2016 Feb
TI  - Role of Growth Arrest and DNA Damage-Inducible, Beta in Alcohol-Drinking 
      Behaviors.
PG  - 263-72
LID - 10.1111/acer.12965 [doi]
AB  - BACKGROUND: The contribution of epigenetic factors, such as histone acetylation 
      and DNA methylation, to the regulation of alcohol-drinking behavior has been 
      increasingly recognized over the last several years. GADD45b is a protein 
      demonstrated to be involved in DNA demethylation at neurotrophic factor gene 
      promoters, including at brain-derived neurotrophic factor (Bdnf) which has been 
      highly implicated in alcohol-drinking behavior. METHODS: DNA methyltransferase-1 
      (Dnmt1), 3a, and 3b, and Gadd45a, b, and g mRNA were measured in the nucleus 
      accumbens (NAc) and ventral tegmental areas of high ethanol (EtOH) consuming 
      C57BL/6J (C57) and low alcohol consuming DBA/2J (DBA) mice using quantitative 
      reverse transcriptase polymerase chain reaction (PCR). In the NAc, GADD45b 
      protein was measured via immunohistochemistry and Bdnf9a mRNA using in situ PCR. 
      Bdnf9a promoter histone H3 acetylated at lysines 9 and 14 (H3K9,K14ac) was 
      measured using chromatin immunoprecipitation, and 5-methylcytosine (5MC) and 
      5-hydroxymethylcytosine (5HMC) using methylated DNA immunoprecipitation. 
      Alcohol-drinking behavior was evaluated in Gadd45b haplodeficient (+/-) and null 
      mice (-/-) utilizing drinking-in-the-dark (DID) and 2-bottle free-choice 
      paradigms. RESULTS: C57 mice had lower levels of Gadd45b and g mRNA and GADD45b 
      protein in the NAc relative to the DBA strain. C57 mice had lower NAc shell 
      Bdnf9a mRNA levels, Bdnf9a promoter H3K9,K14ac, and higher Bdnf9a promoter 5HMC 
      and 5MC. Acute EtOH increased GADD45b protein, Bdnf9a mRNA, and histone 
      acetylation and decreased 5HMC in C57 mice. Gadd45b +/- mice displayed higher 
      drinking behavior relative to wild-type littermates in both DID and 2-bottle 
      free-choice paradigms. CONCLUSIONS: These data indicate the importance of the DNA 
      demethylation pathway and its interactions with histone posttranslational 
      modifications in alcohol-drinking behavior. Further, we suggest that lower DNA 
      demethylation protein GADD45b levels may affect Bdnf expression possibly leading 
      to altered alcohol-drinking behavior.
CI  - Copyright (c) 2016 by the Research Society on Alcoholism.
FAU - Gavin, David P
AU  - Gavin DP
AD  - Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, Illinois.
FAU - Kusumo, Handojo
AU  - Kusumo H
AD  - Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, Illinois.
FAU - Zhang, Huaibo
AU  - Zhang H
AD  - Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, Illinois.
FAU - Guidotti, Alessandro
AU  - Guidotti A
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, Illinois.
FAU - Pandey, Subhash C
AU  - Pandey SC
AD  - Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, Illinois.
LA  - eng
GR  - R29 AA010005/AA/NIAAA NIH HHS/United States
GR  - IK2 BX001650/BX/BLRD VA/United States
GR  - AA022538/AA/NIAAA NIH HHS/United States
GR  - I01 BX000143/BX/BLRD VA/United States
GR  - AA-010005/AA/NIAAA NIH HHS/United States
GR  - R01 AA021662/AA/NIAAA NIH HHS/United States
GR  - R01 MH093348/MH/NIMH NIH HHS/United States
GR  - AA-0212662/AA/NIAAA NIH HHS/United States
GR  - R01 AA010005/AA/NIAAA NIH HHS/United States
GR  - P50 AA022538/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Gadd45b protein, mouse)
SB  - IM
MH  - Alcohol Drinking/*physiopathology
MH  - Animals
MH  - Antigens, Differentiation/analysis/*physiology
MH  - Brain-Derived Neurotrophic Factor/metabolism/physiology
MH  - Epigenesis, Genetic
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mice, Knockout
MH  - Nucleus Accumbens/chemistry
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC4743544
MID - NIHMS740795
OTO - NOTNLM
OT  - Alcoholism
OT  - Bdnf
OT  - DNA Methylation
OT  - GADD45b
OT  - Histone
OT  - Nucleus Accumbens
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2016/02/05 06:00
MHDA- 2016/11/01 06:00
PMCR- 2017/02/01
CRDT- 2016/02/05 06:00
PHST- 2015/09/17 00:00 [received]
PHST- 2015/11/13 00:00 [accepted]
PHST- 2016/02/05 06:00 [entrez]
PHST- 2016/02/05 06:00 [pubmed]
PHST- 2016/11/01 06:00 [medline]
PHST- 2017/02/01 00:00 [pmc-release]
AID - 10.1111/acer.12965 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2016 Feb;40(2):263-72. doi: 10.1111/acer.12965.