MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation
In: Cell Reports, Jg. 35 (2021-04-01), S. 108946-108946
Online
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Zugriff:
SUMMARY Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal brain maturation are less understood. Here, we identify the miR-29 family to be strikingly induced during the late stages of brain maturation. Brain maturation is associated with a transient, postnatal period of de novo non-CG (CH) DNA methylation mediated by DNMT3A. We examine whether an important function of miR-29 during brain maturation is to restrict the period of CH methylation via its targeting of Dnmt3a. Deletion of miR-29 in the brain, or knockin mutations preventing miR-29 to specifically target Dnmt3a, result in increased DNMT3A expression, higher CH methylation, and repression of genes associated with neuronal activity and neuropsychiatric disorders. These mouse models also develop neurological deficits and premature lethality. Our results identify an essential role for miR-29 in restricting CH methylation in the brain and illustrate the importance of CH methylation regulation for normal brain maturation.
Graphical abstract
In brief Non-canonical CH methylation mediated by DNMT3A during neuronal maturation has been recently shown to be critical for brain homeostasis. Swahari et al. identify a key player that is critical for regulating CH methylation: the microRNA miR-29. Failure of miR-29 to regulate the expression of Dnmt3a leads to severe neurobehavioral consequences.
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MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation
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Autor/in / Beteiligte Person: | C. Lisa Kurtz ; Stroud, Hume ; Hammond, Scott M. ; Beck, Matthew V. ; Plestant, Charlotte ; Deshmukh, Mohanish ; Swahari, Vijay ; Simon, Jeremy M. ; Flowers, Cornelius ; Anton, E.S. ; Sethupathy, Praveen ; He, You-Wen ; Ptacek, Travis S. ; Hollville, Emilie ; Greenberg, Michael E. ; Liang, Jie ; Nakamura, Ayumi ; Guo, Jiami ; Kanke, Matt ; Moy, Sheryl S. |
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Zeitschrift: | Cell Reports, Jg. 35 (2021-04-01), S. 108946-108946 |
Veröffentlichung: | Elsevier BV, 2021 |
Medientyp: | unknown |
ISSN: | 2211-1247 (print) |
DOI: | 10.1016/j.celrep.2021.108946 |
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