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Article

The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

1
Interdisciplinary Centre for Bioinformatics, Universität Leipzig, Härtelstr. 16–18, 04107 Leipzig, Germany
2
Institute of Molecular Biology, the National Academy of Sciences of the Republic of Armenia, 7 Hasratyan Str., Yerevan 0014, Armenia
3
Institute of Biomedicine and Pharmacy, Russian-Armenian University, 123 Hovsep Emin Str., Yerevan 0051, Armenia
4
Armenian Bioinformatics Institute (ABI), 7 Hasratyan Str., Yerevan 0014, Armenia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Luisa Alexandra Meireles Pinto
Cells 2022, 11(3), 362; https://doi.org/10.3390/cells11030362
Received: 13 December 2021 / Revised: 15 January 2022 / Accepted: 18 January 2022 / Published: 21 January 2022
(This article belongs to the Special Issue Frontiers in Neurogenesis)
Mutually linked expression and methylation dynamics in the brain govern genome regulation over the whole lifetime with an impact on cognition, psychological disorders, and cancer. We performed a joint study of gene expression and DNA methylation of brain tissue originating from the human prefrontal cortex of individuals across the lifespan to describe changes in cellular programs and their regulation by epigenetic mechanisms. The analysis considers previous knowledge in terms of functional gene signatures and chromatin states derived from independent studies, aging profiles of a battery of chromatin modifying enzymes, and data of gliomas and neuropsychological disorders for a holistic view on the development and aging of the brain. Expression and methylation changes from babies to elderly adults decompose into different modes associated with the serial activation of (brain) developmental, learning, metabolic and inflammatory functions, where methylation in gene promoters mostly represses transcription. Expression of genes encoding methylome modifying enzymes is very diverse reflecting complex regulations during lifetime which also associates with the marked remodeling of chromatin between permissive and restrictive states. Data of brain cancer and psychotic disorders reveal footprints of pathophysiologies related to brain development and aging. Comparison of aging brains with gliomas supports the view that glioblastoma-like and astrocytoma-like tumors exhibit higher cellular plasticity activated in the developing healthy brain while oligodendrogliomas have a more stable differentiation hierarchy more resembling the aged brain. The balance and specific shifts between volatile and stable and between more irreversible and more plastic epigenomic networks govern the development and aging of healthy and diseased brain. View Full-Text
Keywords: human brain; development and aging; gene expression; DNA methylation; chromatin remodeling; epigenetics; bioinformatics; machine learning human brain; development and aging; gene expression; DNA methylation; chromatin remodeling; epigenetics; bioinformatics; machine learning
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MDPI and ACS Style

Loeffler-Wirth, H.; Hopp, L.; Schmidt, M.; Zakharyan, R.; Arakelyan, A.; Binder, H. The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders. Cells 2022, 11, 362. https://doi.org/10.3390/cells11030362

AMA Style

Loeffler-Wirth H, Hopp L, Schmidt M, Zakharyan R, Arakelyan A, Binder H. The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders. Cells. 2022; 11(3):362. https://doi.org/10.3390/cells11030362

Chicago/Turabian Style

Loeffler-Wirth, Henry, Lydia Hopp, Maria Schmidt, Roksana Zakharyan, Arsen Arakelyan, and Hans Binder. 2022. "The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders" Cells 11, no. 3: 362. https://doi.org/10.3390/cells11030362

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