PMID- 34960080
OWN - NLM
STAT- MEDLINE
DCOM- 20220114
LR  - 20230221
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 13
IP  - 12
DP  - 2021 Dec 17
TI  - Prenatal Iron Deficiency and Choline Supplementation Interact to Epigenetically 
      Regulate Jarid1b and Bdnf in the Rat Hippocampus into Adulthood.
LID - 10.3390/nu13124527 [doi]
LID - 4527
AB  - Early-life iron deficiency (ID) causes long-term neurocognitive impairments and 
      gene dysregulation that can be partially mitigated by prenatal choline 
      supplementation. The long-term gene dysregulation is hypothesized to underlie 
      cognitive dysfunction. However, mechanisms by which iron and choline mediate 
      long-term gene dysregulation remain unknown. In the present study, using a 
      well-established rat model of fetal-neonatal ID, we demonstrated that ID 
      downregulated hippocampal expression of the gene encoding JmjC-ARID 
      domain-containing protein 1B (JARID1B), an iron-dependent histone H3K4 
      demethylase, associated with a higher histone deacetylase 1 (HDAC1) enrichment 
      and a lower enrichment of acetylated histone H3K9 (H3K9ac) and phosphorylated 
      cAMP response element-binding protein (pCREB). Likewise, ID reduced 
      transcriptional capacity of the gene encoding brain-derived neurotrophic factor 
      (BDNF), a target of JARID1B, associated with repressive histone modifications 
      such as lower H3K9ac and pCREB enrichments at the Bdnf promoters in the adult rat 
      hippocampus. Prenatal choline supplementation did not prevent the ID-induced 
      chromatin modifications at these loci but induced long-lasting repressive 
      chromatin modifications in the iron-sufficient adult rats. Collectively, these 
      findings demonstrated that the iron-dependent epigenetic mechanism mediated by 
      JARID1B accounted for long-term Bdnf dysregulation by early-life ID. Choline 
      supplementation utilized a separate mechanism to rescue the effect of ID on 
      neural gene regulation. The negative epigenetic effects of choline 
      supplementation in the iron-sufficient rat hippocampus necessitate additional 
      investigations prior to its use as an adjunctive therapeutic agent.
FAU - Liu, Shirelle X
AU  - Liu SX
AUID- ORCID: 0000-0003-2550-008X
AD  - Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
AD  - Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA.
FAU - Barks, Amanda K
AU  - Barks AK
AD  - Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
FAU - Lunos, Scott
AU  - Lunos S
AD  - Biostatistical Design and Analysis Center, Clinical and Translational Science 
      Institute, University of Minnesota, Minneapolis, MN 55455, USA.
FAU - Gewirtz, Jonathan C
AU  - Gewirtz JC
AD  - Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA.
FAU - Georgieff, Michael K
AU  - Georgieff MK
AD  - Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
FAU - Tran, Phu V
AU  - Tran PV
AUID- ORCID: 0000-0002-4301-941X
AD  - Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
LA  - eng
GR  - R01 NS099178/NS/NINDS NIH HHS/United States
GR  - UL1TR002494/NH/NIH HHS/United States
GR  - R01HD29421/NH/NIH HHS/United States
GR  - R01NS099178/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20211217
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Repressor Proteins)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
RN  - EC 1.14.11.- (Kdm5b protein, rat)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Choline/administration & dosage/*pharmacology
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Dietary Supplements
MH  - Epigenesis, Genetic
MH  - Female
MH  - Hippocampus/*drug effects/metabolism
MH  - *Iron Deficiencies
MH  - Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Repressor Proteins/*metabolism
PMC - PMC8706459
OTO - NOTNLM
OT  - Bdnf
OT  - Jarid1b
OT  - choline
OT  - epigenetics
OT  - gene expression
OT  - histone modification
OT  - iron deficiency
COIS- The authors declare that they have no conflict of interest with the contents of 
      this article.
EDAT- 2021/12/29 06:00
MHDA- 2022/01/15 06:00
PMCR- 2021/12/17
CRDT- 2021/12/28 01:05
PHST- 2021/11/19 00:00 [received]
PHST- 2021/12/10 00:00 [revised]
PHST- 2021/12/14 00:00 [accepted]
PHST- 2021/12/28 01:05 [entrez]
PHST- 2021/12/29 06:00 [pubmed]
PHST- 2022/01/15 06:00 [medline]
PHST- 2021/12/17 00:00 [pmc-release]
AID - nu13124527 [pii]
AID - nutrients-13-04527 [pii]
AID - 10.3390/nu13124527 [doi]
PST - epublish
SO  - Nutrients. 2021 Dec 17;13(12):4527. doi: 10.3390/nu13124527.