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The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders
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Genes 2017, 8(5), 137; doi:10.3390/genes8050137

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure

1
Jesse Brown Veterans Affairs Medical Center, 820 South Damen Avenue (M/C 151), Chicago, IL 60612, USA
2
Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612, USA
3
Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road L470, Portland, OR 97239, USA
4
Veterans Affairs Portland Health Care System, 3710 Southwest US Veterans Hospital Road, Portland, OR 97239, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Roel Ophoff
Received: 31 January 2017 / Revised: 1 May 2017 / Accepted: 6 May 2017 / Published: 11 May 2017
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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Abstract

Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications. However, the data linking alcohol-induced differentiation changes with developmental alterations in chromatin structure remain to be elucidated. In the first part of this review, we discuss the sequence of chromatin structural changes involved in neural cell differentiation during normal development. We then discuss the effects of prenatal alcohol on developmental histone modifications and DNA methylation in the context of neurogenesis and astrogliogenesis. We attempt to synthesize the developmental literature with the FASD literature, proposing that alcohol-induced changes to chromatin structure account for altered neurogenesis and astrogliogenesis as well as altered neuron and astrocyte differentiation. Together these changes may contribute to the cognitive and behavioral abnormalities in FASD. Future studies using standardized alcohol exposure paradigms at specific developmental stages will advance the understanding of how chromatin structural changes impact neural cell fate and maturation in FASD. View Full-Text
Keywords: histone modifications; DNA methylation; fetal alcohol; neural cell differentiation; neurons; astrocytes; chromatin histone modifications; DNA methylation; fetal alcohol; neural cell differentiation; neurons; astrocytes; chromatin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Gavin, D.P.; Grayson, D.R.; Varghese, S.P.; Guizzetti, M. Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure. Genes 2017, 8, 137.

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