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Biology 2019, 8(1), 11; https://doi.org/10.3390/biology8010011

Histone 4 Lysine 20 Methylation: A Case for Neurodevelopmental Disease

Department of Pharmacology, School of Medicine, Creighton University, Omaha, NE 68178, USA
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Received: 28 December 2018 / Revised: 22 February 2019 / Accepted: 26 February 2019 / Published: 3 March 2019
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Abstract

Neurogenesis is an elegantly coordinated developmental process that must maintain a careful balance of proliferation and differentiation programs to be compatible with life. Due to the fine-tuning required for these processes, epigenetic mechanisms (e.g., DNA methylation and histone modifications) are employed, in addition to changes in mRNA transcription, to regulate gene expression. The purpose of this review is to highlight what we currently know about histone 4 lysine 20 (H4K20) methylation and its role in the developing brain. Utilizing publicly-available RNA-Sequencing data and published literature, we highlight the versatility of H4K20 methyl modifications in mediating diverse cellular events from gene silencing/chromatin compaction to DNA double-stranded break repair. From large-scale human DNA sequencing studies, we further propose that the lysine methyltransferase gene, KMT5B (OMIM: 610881), may fit into a category of epigenetic modifier genes that are critical for typical neurodevelopment, such as EHMT1 and ARID1B, which are associated with Kleefstra syndrome (OMIM: 610253) and Coffin-Siris syndrome (OMIM: 135900), respectively. Based on our current knowledge of the H4K20 methyl modification, we discuss emerging themes and interesting questions on how this histone modification, and particularly KMT5B expression, might impact neurodevelopment along with current challenges and potential avenues for future research. View Full-Text
Keywords: H4K20; KMT5A; KMT5B; KMT5C; SUV420H; lysine-methylation; neurodevelopment; mutations; epigenetic; histone methylation H4K20; KMT5A; KMT5B; KMT5C; SUV420H; lysine-methylation; neurodevelopment; mutations; epigenetic; histone methylation
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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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Wickramasekara, R.N.; Stessman, H.A.F. Histone 4 Lysine 20 Methylation: A Case for Neurodevelopmental Disease. Biology 2019, 8, 11.

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