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Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice. / Ershov, Nikita I.; Bondar, Natalya P.; Lepeshko, Arina A. et al.
In: BMC Genomics, Vol. 19, No. Suppl 3, 93, 09.02.2018, p. 93.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice
AU - Ershov, Nikita I.
AU - Bondar, Natalya P.
AU - Lepeshko, Arina A.
AU - Reshetnikov, Vasiliy V.
AU - Ryabushkina, Julia A.
AU - Merkulova, Tatiana I.
N1 - Publisher Copyright: © 2018 The Author(s).
PY - 2018/2/9
Y1 - 2018/2/9
N2 - Background: Maternal separation models in rodents are widely used to establish molecular mechanisms underlying prolonged effects of early life adversity on neurobiological and behavioral outcomes in adulthood. However, global epigenetic signatures following early life stress in these models remain unclear. Results: In this study, we carried out a ChIP-seq analysis of H3K4 trimethylation profile in the prefrontal cortex of adult male mice with a history of early life stress. Two types of stress were used: prolonged separation of pups from their mothers (for 3 h once a day, maternal separation, MS) and brief separation (for 15 min once a day, handling, HD). Adult offspring in the MS group demonstrated reduced locomotor activity in the open field test accompanied by reduced exploratory activity, while the HD group showed decreased anxiety-like behavior only. In a group of maternal separation, we have found a small number (45) of slightly up-regulated peaks, corresponding to promoters of 70 genes, while no changes were observed in a group of handling. Among the genes whose promoters have differential enrichment of H3K4me3, the most relevant ones participate in gene expression regulation, modulation of chromatin structure and mRNA processing. For two genes, Ddias and Pip4k2a, increased H3K4me3 levels were associated with the increased mRNA expression in MS group. Conclusion: The distribution of H3K4me3 in prefrontal cortex showed relatively low variability across all individuals, and only some subtle changes were revealed in mice with a history of early life stress. It is possible that the observed long-lasting behavioral alterations induced by maternal separation are mediated by other epigenetic mechanisms, or other brain structures are responsible for these effects.
AB - Background: Maternal separation models in rodents are widely used to establish molecular mechanisms underlying prolonged effects of early life adversity on neurobiological and behavioral outcomes in adulthood. However, global epigenetic signatures following early life stress in these models remain unclear. Results: In this study, we carried out a ChIP-seq analysis of H3K4 trimethylation profile in the prefrontal cortex of adult male mice with a history of early life stress. Two types of stress were used: prolonged separation of pups from their mothers (for 3 h once a day, maternal separation, MS) and brief separation (for 15 min once a day, handling, HD). Adult offspring in the MS group demonstrated reduced locomotor activity in the open field test accompanied by reduced exploratory activity, while the HD group showed decreased anxiety-like behavior only. In a group of maternal separation, we have found a small number (45) of slightly up-regulated peaks, corresponding to promoters of 70 genes, while no changes were observed in a group of handling. Among the genes whose promoters have differential enrichment of H3K4me3, the most relevant ones participate in gene expression regulation, modulation of chromatin structure and mRNA processing. For two genes, Ddias and Pip4k2a, increased H3K4me3 levels were associated with the increased mRNA expression in MS group. Conclusion: The distribution of H3K4me3 in prefrontal cortex showed relatively low variability across all individuals, and only some subtle changes were revealed in mice with a history of early life stress. It is possible that the observed long-lasting behavioral alterations induced by maternal separation are mediated by other epigenetic mechanisms, or other brain structures are responsible for these effects.
KW - ChIP-seq
KW - Early life stress
KW - H3K4me3
KW - Handling
KW - Maternal separation
KW - Mice
KW - Prefrontal cortex
KW - Lysine/metabolism
KW - Genomics
KW - Mice, Inbred C57BL
KW - Prefrontal Cortex/metabolism
KW - Male
KW - Emotions
KW - Behavior, Animal
KW - Maternal Deprivation
KW - Stress, Psychological/genetics
KW - Animals
KW - Histones/chemistry
KW - Female
KW - Methylation
KW - Adaptation, Psychological
KW - RATS
KW - HISTONE CHAPERONE SPT6
KW - BRAIN
KW - ANXIETY
KW - BEHAVIOR
KW - C57BL/6 MICE
KW - MAMMALIAN GENOMES
KW - MATERNAL SEPARATION
KW - GENE
KW - WORKING-MEMORY
UR - http://www.scopus.com/inward/record.url?scp=85041857415&partnerID=8YFLogxK
U2 - 10.1186/s12864-018-4479-2
DO - 10.1186/s12864-018-4479-2
M3 - Article
C2 - 29504911
AN - SCOPUS:85041857415
VL - 19
SP - 93
JO - BMC Genomics
JF - BMC Genomics
SN - 1471-2164
IS - Suppl 3
M1 - 93
ER -
ID: 10422519