TY - JOUR

T1 - Aberrant DNA methylation in lymphocytes of children with neurodevelopmental disorders

AU - Naumova, O. Yu

AU - Rychkov, S. Yu

AU - Odintsova, V. V.

AU - Kornilov, S. A.

AU - Shabalina, E. V.

AU - Antsiferova, D. V.

AU - Zhukova, O. V.

AU - Grigorenko, E. L.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Recent research in the field of genomics and epigenetics has provided evidence that alterations in the system of epigenetic regulation are highly involved in the molecular etiology of neurodegenerative and neuropathic disorders. However, there is a gap in knowledge on the epigenetic perturbations that may accompany the CNS impairments during the development in the prenatal period and their manifestation as a congenital encephalopathy in the early postnatal period of child development. The present study is one of the first attempts aimed at addressing this gap. Here, we present data on genome-wide profiles of DNA methylation obtained using the Illumina HumanMethylation450 microarray in peripheral blood cells in a sample of young children (up to four years of age) diagnosed with congenital encephalopathy. We provide evidence on systematic alterations in the epigenome—predominant hypermethylation of gene promoter associated CpG islands—related to the CNS impairment in children. Specifically, we found significant DNA methylation changes in genes involved in DNA-dependent transcription regulation and transcription factor binding, with a key role of the transcription factor JUN; in genes controlling cellular response to hypoxia; and in genes involved in the control of neuronal development, functioning, and death.

AB - Recent research in the field of genomics and epigenetics has provided evidence that alterations in the system of epigenetic regulation are highly involved in the molecular etiology of neurodegenerative and neuropathic disorders. However, there is a gap in knowledge on the epigenetic perturbations that may accompany the CNS impairments during the development in the prenatal period and their manifestation as a congenital encephalopathy in the early postnatal period of child development. The present study is one of the first attempts aimed at addressing this gap. Here, we present data on genome-wide profiles of DNA methylation obtained using the Illumina HumanMethylation450 microarray in peripheral blood cells in a sample of young children (up to four years of age) diagnosed with congenital encephalopathy. We provide evidence on systematic alterations in the epigenome—predominant hypermethylation of gene promoter associated CpG islands—related to the CNS impairment in children. Specifically, we found significant DNA methylation changes in genes involved in DNA-dependent transcription regulation and transcription factor binding, with a key role of the transcription factor JUN; in genes controlling cellular response to hypoxia; and in genes involved in the control of neuronal development, functioning, and death.

KW - differential methylation

KW - encephalopathy

KW - epigenetics

KW - genome-wide DNA methylation

KW - Illumina HumanMethylation450

KW - peripheral blood lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=85036632421&partnerID=8YFLogxK

U2 - 10.1134/S1022795417110072

DO - 10.1134/S1022795417110072

M3 - Article

AN - SCOPUS:85036632421

VL - 53

SP - 1243

EP - 1258

JO - Russian Journal of Genetics

JF - Russian Journal of Genetics

SN - 1022-7954

IS - 11

ER -