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Review
. 2018 May 1;19(5):1333.
doi: 10.3390/ijms19051333.

The Vast Complexity of the Epigenetic Landscape during Neurodevelopment: An Open Frame to Understanding Brain Function

Ariel Ernesto Cariaga-Martínez  1 , Kilian Jesús Gutiérrez  2 , Raúl Alelú-Paz  3
Affiliations
Review

The Vast Complexity of the Epigenetic Landscape during Neurodevelopment: An Open Frame to Understanding Brain Function

Ariel Ernesto Cariaga-Martínez et al. Int J Mol Sci. .

Abstract

Development is a well-defined stage-to-stage process that allows the coordination and maintenance of the structure and function of cells and their progenitors, in a complete organism embedded in an environment that, in turn, will shape cellular responses to external stimuli. Epigenetic mechanisms comprise a group of process that regulate genetic expression without changing the DNA sequence, and they contribute to the necessary plasticity of individuals to face a constantly changing medium. These mechanisms act in conjunction with genetic pools and their correct interactions will be crucial to zygote formation, embryo development, and brain tissue organization. In this work, we will summarize the main findings related to DNA methylation and histone modifications in embryonic stem cells and throughout early development phases. Furthermore, we will critically outline some key observations on how epigenetic mechanisms influence the rest of the developmental process and how long its footprint is extended from fecundation to adulthood.

Keywords: DNA methylation; brain; development; epigenetic; histone modifications; neuroepigenome.

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Conflict of interest statement

The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Pathways in the biogenesis of cytosine methylation in its intermediaries. C = Cytosine. 5mC = 5-methylcytosine. 5hmC = 5-hydroxymethycytosine. 5fC = 5-formilcytosine. 5caC = 5-carboxylcytosine. 5hmU = 5-hydroxymethyluracyl. T = Thymine. DNMT = DNA methyltransferases. TDG = Thymine DNA glycosylase. BER = Base excision repair system. AID = activation induced deaminase. APOBEC = Apolipoprotein B mRNA editing enzyme, catalytic polypeptide.
Figure 2
Figure 2
Summary of DNA methylation characteristics for cell types throughout development. Please see text for further details.
Figure 3
Figure 3
The presence of bivalent domains in ES cells is essential for maintaining a poised state. After lineage commitment, several histone erasers and writers will change the histone PTM in concordance with TET enzymes that will modify the DNA methylation status (shown as red dots). This plethora of epigenetic changes will also contribute to the expression of development-related genes. In an adult cell, repressive complexes and DNA hyper-methylation will lead to a “closed” chromatin state, avoiding the expression of development-related genes, and keeping the tissue’s identity.
See this image and copyright information in PMC

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