Cellular DNA methylation program during neurulation and its alteration by alcohol exposure

Feng Zhou, Yuanyuan Chen, Ada Love

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

BACKGROUND: Epigenetic changes are believed to be among the earliest key regulators for cell fate and embryonic development. To support this premise, it is important to understand whether or not systemic epigenetic changes coordinate with the progression of development. We have demonstrated that DNA methylation is programmed when neural stem cells differentiate (Zhou et al.,2011). Here, we analyzed the DNA methylation events that occur during early neural tube development. METHODS AND RESULTS Using immunocytochemistry, we demonstrated that the DNA methylation marks - 5-methylcytosine (5-MeC), DNA methylation binding domain 1 (MBD1), and DNA methytransferases 1 (DNMT1) were highly coordinated in temporal and spatial patterns that paralleled the progress of embryonic development. The above ontogenic program of DNA methylation was, however, subjected to environmental modification. Alcohol exposure during fetal development, which is known to cause fetal alcohol spectrum disorder, altered the density and distribution of the DNA methylation marks. The alcohol exposure (88 mM) over 6 or 44 hours at gestation day 8 (GD-8) to GD-10 altered timely DNA methylation and retarded embryonic growth. We further demonstrated that the direct inhibiting of DNA methylation with 5-aza-cytidine (5-AZA) resulted in similar growth retardation. CONCLUSIONS We identified a temporal and spatial cellular DNA methylation program after initial erasure, which parallels embryonic maturation. Alcohol delayed the cellular DNA methylation program and also retarded embryonic growth. Since direct inhibiting of DNA methylation resulted in similar retardation, alcohol thus can affect embryonic development through a epigenetic pathway.

Original languageEnglish
Pages (from-to)703-715
Number of pages13
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume91
Issue number8
DOIs
StatePublished - Aug 2011

Fingerprint

Neurulation
DNA Methylation
Alcohols
Epigenomics
Embryonic Development
Growth
5-Methylcytosine
Fetal Alcohol Spectrum Disorders
Cytidine
Neural Tube
Neural Stem Cells
Fetal Development

Keywords

  • Differentiation
  • DNMT
  • Epigenetics
  • Fetal alcohol syndrome
  • MBD1
  • Neural crest
  • Neural tube

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health
  • Embryology

Cite this

Cellular DNA methylation program during neurulation and its alteration by alcohol exposure. / Zhou, Feng; Chen, Yuanyuan; Love, Ada.

In: Birth Defects Research Part A - Clinical and Molecular Teratology, Vol. 91, No. 8, 08.2011, p. 703-715.

Research output: Contribution to journalArticle

@article{eb8d6a9552c34e9c8e32c9f8e896c212,
title = "Cellular DNA methylation program during neurulation and its alteration by alcohol exposure",
abstract = "BACKGROUND: Epigenetic changes are believed to be among the earliest key regulators for cell fate and embryonic development. To support this premise, it is important to understand whether or not systemic epigenetic changes coordinate with the progression of development. We have demonstrated that DNA methylation is programmed when neural stem cells differentiate (Zhou et al.,2011). Here, we analyzed the DNA methylation events that occur during early neural tube development. METHODS AND RESULTS Using immunocytochemistry, we demonstrated that the DNA methylation marks - 5-methylcytosine (5-MeC), DNA methylation binding domain 1 (MBD1), and DNA methytransferases 1 (DNMT1) were highly coordinated in temporal and spatial patterns that paralleled the progress of embryonic development. The above ontogenic program of DNA methylation was, however, subjected to environmental modification. Alcohol exposure during fetal development, which is known to cause fetal alcohol spectrum disorder, altered the density and distribution of the DNA methylation marks. The alcohol exposure (88 mM) over 6 or 44 hours at gestation day 8 (GD-8) to GD-10 altered timely DNA methylation and retarded embryonic growth. We further demonstrated that the direct inhibiting of DNA methylation with 5-aza-cytidine (5-AZA) resulted in similar growth retardation. CONCLUSIONS We identified a temporal and spatial cellular DNA methylation program after initial erasure, which parallels embryonic maturation. Alcohol delayed the cellular DNA methylation program and also retarded embryonic growth. Since direct inhibiting of DNA methylation resulted in similar retardation, alcohol thus can affect embryonic development through a epigenetic pathway.",
keywords = "Differentiation, DNMT, Epigenetics, Fetal alcohol syndrome, MBD1, Neural crest, Neural tube",
author = "Feng Zhou and Yuanyuan Chen and Ada Love",
year = "2011",
month = "8",
doi = "10.1002/bdra.20820",
language = "English",
volume = "91",
pages = "703--715",
journal = "Teratology",
issn = "1542-0752",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Cellular DNA methylation program during neurulation and its alteration by alcohol exposure

AU - Zhou, Feng

AU - Chen, Yuanyuan

AU - Love, Ada

PY - 2011/8

Y1 - 2011/8

N2 - BACKGROUND: Epigenetic changes are believed to be among the earliest key regulators for cell fate and embryonic development. To support this premise, it is important to understand whether or not systemic epigenetic changes coordinate with the progression of development. We have demonstrated that DNA methylation is programmed when neural stem cells differentiate (Zhou et al.,2011). Here, we analyzed the DNA methylation events that occur during early neural tube development. METHODS AND RESULTS Using immunocytochemistry, we demonstrated that the DNA methylation marks - 5-methylcytosine (5-MeC), DNA methylation binding domain 1 (MBD1), and DNA methytransferases 1 (DNMT1) were highly coordinated in temporal and spatial patterns that paralleled the progress of embryonic development. The above ontogenic program of DNA methylation was, however, subjected to environmental modification. Alcohol exposure during fetal development, which is known to cause fetal alcohol spectrum disorder, altered the density and distribution of the DNA methylation marks. The alcohol exposure (88 mM) over 6 or 44 hours at gestation day 8 (GD-8) to GD-10 altered timely DNA methylation and retarded embryonic growth. We further demonstrated that the direct inhibiting of DNA methylation with 5-aza-cytidine (5-AZA) resulted in similar growth retardation. CONCLUSIONS We identified a temporal and spatial cellular DNA methylation program after initial erasure, which parallels embryonic maturation. Alcohol delayed the cellular DNA methylation program and also retarded embryonic growth. Since direct inhibiting of DNA methylation resulted in similar retardation, alcohol thus can affect embryonic development through a epigenetic pathway.

AB - BACKGROUND: Epigenetic changes are believed to be among the earliest key regulators for cell fate and embryonic development. To support this premise, it is important to understand whether or not systemic epigenetic changes coordinate with the progression of development. We have demonstrated that DNA methylation is programmed when neural stem cells differentiate (Zhou et al.,2011). Here, we analyzed the DNA methylation events that occur during early neural tube development. METHODS AND RESULTS Using immunocytochemistry, we demonstrated that the DNA methylation marks - 5-methylcytosine (5-MeC), DNA methylation binding domain 1 (MBD1), and DNA methytransferases 1 (DNMT1) were highly coordinated in temporal and spatial patterns that paralleled the progress of embryonic development. The above ontogenic program of DNA methylation was, however, subjected to environmental modification. Alcohol exposure during fetal development, which is known to cause fetal alcohol spectrum disorder, altered the density and distribution of the DNA methylation marks. The alcohol exposure (88 mM) over 6 or 44 hours at gestation day 8 (GD-8) to GD-10 altered timely DNA methylation and retarded embryonic growth. We further demonstrated that the direct inhibiting of DNA methylation with 5-aza-cytidine (5-AZA) resulted in similar growth retardation. CONCLUSIONS We identified a temporal and spatial cellular DNA methylation program after initial erasure, which parallels embryonic maturation. Alcohol delayed the cellular DNA methylation program and also retarded embryonic growth. Since direct inhibiting of DNA methylation resulted in similar retardation, alcohol thus can affect embryonic development through a epigenetic pathway.

KW - Differentiation

KW - DNMT

KW - Epigenetics

KW - Fetal alcohol syndrome

KW - MBD1

KW - Neural crest

KW - Neural tube

UR - http://www.scopus.com/inward/record.url?scp=79961135015&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961135015&partnerID=8YFLogxK

U2 - 10.1002/bdra.20820

DO - 10.1002/bdra.20820

M3 - Article

C2 - 21630420

AN - SCOPUS:79961135015

VL - 91

SP - 703

EP - 715

JO - Teratology

JF - Teratology

SN - 1542-0752

IS - 8

ER -