The Interplay between DNA Methylation, Folate and Neurocognitive Development

Abstract

DNA methylation provides an attractive possible means for propagating the effects of environmental inputs during fetal life and impacting subsequent adult mental health, which is leading to increasing collaboration between molecular biologists, nutritionists and psychiatrists. An area of interest is the potential role of folate, not just in neural tube closure in early pregnancy, but in later major neurodevelopmental events, with consequences for later sociocognitive maturation. Here, we set the scene for recent discoveries by reviewing the major events of neural development during fetal life, with an emphasis on tissues and structures where dynamic methylation changes are known to occur. Following this, we give an indication of some of the major classes of genes targeted by methylation and important for neurological and behavioral development. Finally, we highlight some cognitive disorders where methylation changes are implicated as playing an important role.

Keywords::

• 5-hydroxymethylation
• Barker hypothesis
• DNMT1
• DNMT3A
• homocysteine
• MeCP2
• TET

Acknowledgements

The authors are grateful to A Caffrey and L-A Henry for valuable discussions.

Financial & competing interests disclosure

Work in the authors’ laboratories is supported by an Enabling Research Award STL/5043/14) from the HSC Research and Development Division of the Public Health Agency, Northern Ireland (to K Pentieva, CP Walsh and H McNulty), an MRC project grant (MR/J007773/1 to CP Walsh) and an Epigenetics Initiative grant from the ESRC/BBSRC (the EpiFASSTT study ES/N000323/1 to CP Walsh, K Pentieva, T Cassidy, H McNulty, DL Lees-Murdock, M McLaughlin and G Prasad). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Work in the authors’ laboratories is supported by an Enabling Research Award STL/5043/14) from the HSC Research and Development Division of the Public Health Agency, Northern Ireland (to K Pentieva, CP Walsh and H McNulty), an MRC project grant (MR/J007773/1 to CP Walsh) and an Epigenetics Initiative grant from the ESRC/BBSRC (the EpiFASSTT study ES/N000323/1 to CP Walsh, K Pentieva, T Cassidy, H McNulty, DL Lees-Murdock, M McLaughlin and G Prasad). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.