EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity
| Autor: | Xiaoran Wei, Jianlin He, Ming-an Sun, Alicia M. Pickrell, Zhixiong Sun, Jianjun Chen, Alexander Murray, Alexei Morozov, Xiguang Xu, Michelle H. Theus, Xia Wang, Evan Xie, Jinsong Zhu, Xi Jiang, Liwu Li, Emmarose L. McCoig, Hehuang Xie |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Epigenomics Male General Physics and Astronomy 02 engineering and technology Epigenome Mice Epigenetics in the nervous system lcsh:Science Mice Knockout Neurons Multidisciplinary Neuronal Plasticity Epigenetics and plasticity Brain Methylation 021001 nanoscience & nanotechnology Cell biology DNA-Binding Proteins DNA methylation Models Animal 0210 nano-technology endocrine system Science Neurogenesis Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Proto-Oncogene Proteins Animals Humans Protein Interaction Domains and Motifs Epigenetics Gene Transcription factor Early Growth Response Protein 1 Binding Sites Sequence-Specific DNA Binding Protein General Chemistry DNA Methylation Mice Inbred C57BL 030104 developmental biology DNA demethylation HEK293 Cells Gene Expression Regulation biology.protein Demethylase lcsh:Q Transcriptome Transcription Factors Neuroscience |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-11905-3 |
| Popis: | 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. It is unclear why neuronal activity induced methylation changes are limited to specific loci in the genome. Here, authors show that the DNA demethylation enzyme, TET1, gains its specificity via the interaction with EGR1, a sequence specific DNA binding protein. |
| Databáze: | OpenAIRE |
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