EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity
dc.contributor.author | Sun, Zhixiong | en |
dc.contributor.author | Xu, Xiguang | en |
dc.contributor.author | He, Jianlin | en |
dc.contributor.author | Murray, Alexander | en |
dc.contributor.author | Sun, Ming-an | en |
dc.contributor.author | Wei, Xiaoran | en |
dc.contributor.author | Wang, Xia | en |
dc.contributor.author | McCoig, Emmarose | en |
dc.contributor.author | Xie, Evan | en |
dc.contributor.author | Jiang, Xi | en |
dc.contributor.author | Li, Liwu | en |
dc.contributor.author | Zhu, Jinsong | en |
dc.contributor.author | Chen, Jianjun | en |
dc.contributor.author | Morozov, Alexei | en |
dc.contributor.author | Pickrell, Alicia M. | en |
dc.contributor.author | Theus, Michelle H. | en |
dc.contributor.author | Xie, Hehuang David | en |
dc.contributor.department | Biochemistry | en |
dc.contributor.department | Biological Sciences | en |
dc.contributor.department | Biomedical Sciences and Pathobiology | en |
dc.contributor.department | Fralin Biomedical Research Institute | en |
dc.contributor.department | Fralin Life Sciences Institute | en |
dc.contributor.department | Virginia Tech Carilion School of Medicine | en |
dc.date.accessioned | 2019-10-02T17:27:35Z | en |
dc.date.available | 2019-10-02T17:27:35Z | en |
dc.date.issued | 2019-08-29 | en |
dc.description.abstract | Life experience can leave lasting marks, such as epigenetic changes, in the brain. How life experience is translated into storable epigenetic information remains largely unknown. With unbiased data-driven approaches, we predicted that Egr1, a transcription factor important for memory formation, plays an essential role in brain epigenetic programming. We performed EGR1 ChIP-seq and validated thousands of EGR1 binding sites with methylation patterns established during postnatal brain development. More specifically, these EGR1 binding sites become hypomethylated in mature neurons but remain heavily methylated in glia. We further demonstrated that EGR1 recruits a DNA demethylase TET1 to remove the methylation marks and activate downstream genes. The frontal cortices from the knockout mice lacking Egr1 or Tet1 share strikingly similar profiles in both gene expression and DNA methylation. In summary, our study reveals EGR1 programs the brain methylome together with TET1 providing new insight into how life experience may shape the brain methylome. | en |
dc.description.notes | The authors thank Drs. Joseph, R. Ecker, Ryan Lister, and Eran A. Mukamel for sharing brain methylome data, Drs. Bing Ren and Bradley E Bernstein for sharing ChIP-seq data, and the labs contributing to ENCODE project. This work was supported by NIH grant NS094574, the Fralin Life Sciences Institute faculty development fund for H.X and VT's Open Access Subvention Fund. | en |
dc.description.sponsorship | NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NS094574]; Fralin Life Sciences Institute faculty development fund; VT's Open Access Subvention Fund | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.doi | https://doi.org/10.1038/s41467-019-11905-3 | en |
dc.identifier.issn | 2041-1723 | en |
dc.identifier.other | 3892 | en |
dc.identifier.pmid | 31467272 | en |
dc.identifier.uri | http://hdl.handle.net/10919/94321 | en |
dc.identifier.volume | 10 | en |
dc.language.iso | en | en |
dc.rights | Creative Commons Attribution 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
dc.title | EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity | en |
dc.title.serial | Nature Communications | en |
dc.type | Article - Refereed | en |
dc.type.dcmitype | Text | en |
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