The Epigenetic State of PRDM16-Regulated Enhancers in Radial Glia Controls Cortical Neuron Position

Neuron
José-Manuel BaizabalCorey C Harwell

Abstract

The epigenetic landscape is dynamically remodeled during neurogenesis. However, it is not understood how chromatin modifications in neural stem cells instruct the formation of complex structures in the brain. We report that the histone methyltransferase PRDM16 is required in radial glia to regulate lineage-autonomous and stage-specific gene expression programs that control number and position of upper layer cortical projection neurons. PRDM16 regulates the epigenetic state of transcriptional enhancers to activate genes involved in intermediate progenitor cell production and repress genes involved in cell migration. The histone methyltransferase domain of PRDM16 is necessary in radial glia to promote cortical neuron migration through transcriptional silencing. We show that repression of the gene encoding the E3 ubiquitin ligase PDZRN3 by PRDM16 determines the position of upper layer neurons. These findings provide insights into how epigenetic control of transcriptional enhancers in radial glial determines the organization of the mammalian cerebral cortex.

Citations

Oct 3, 2018·Journal of Neurochemistry·Nicole AmbergSimon Hippenmeyer
Oct 3, 2020·International Journal of Molecular Sciences·Paweł LeszczyńskiHiroaki Taniguchi
Nov 5, 2019·F1000Research·Victor Borrell
Sep 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Whitney E HeavnerSusan K McConnell
Jan 26, 2020·Scientific Reports·Takeshi Honda, Makoto Inui
Feb 12, 2020·Development·Angela ChuiSong-Hai Shi
Dec 8, 2019·Neuron·Tingting WangGraeme W Davis
Mar 29, 2021·The FEBS Journal·Federico Di TullioErnesto Guccione
Dec 2, 2021·ELife·Miguel Turrero GarcíaCorey C Harwell

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