EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity

dc.contributor.authorSun, Zhixiongen
dc.contributor.authorXu, Xiguangen
dc.contributor.authorHe, Jianlinen
dc.contributor.authorMurray, Alexanderen
dc.contributor.authorSun, Ming-anen
dc.contributor.authorWei, Xiaoranen
dc.contributor.authorWang, Xiaen
dc.contributor.authorMcCoig, Emmaroseen
dc.contributor.authorXie, Evanen
dc.contributor.authorJiang, Xien
dc.contributor.authorLi, Liwuen
dc.contributor.authorZhu, Jinsongen
dc.contributor.authorChen, Jianjunen
dc.contributor.authorMorozov, Alexeien
dc.contributor.authorPickrell, Alicia M.en
dc.contributor.authorTheus, Michelle H.en
dc.contributor.authorXie, Hehuang Daviden
dc.contributor.departmentBiochemistryen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.date.accessioned2019-10-02T17:27:35Zen
dc.date.available2019-10-02T17:27:35Zen
dc.date.issued2019-08-29en
dc.description.abstractLife 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.notesThe 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.sponsorshipNIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NS094574]; Fralin Life Sciences Institute faculty development fund; VT's Open Access Subvention Funden
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41467-019-11905-3en
dc.identifier.issn2041-1723en
dc.identifier.other3892en
dc.identifier.pmid31467272en
dc.identifier.urihttp://hdl.handle.net/10919/94321en
dc.identifier.volume10en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleEGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activityen
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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