Postnatal expression of the lysine methyltransferase SETD1B is essential for learning and the regulation of neuron‐enriched genes
2021 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Postnatal expression of the lysine methyltransferase SETD1B is essential for learning and the regulation of neuron‐enriched genes
Michurina, A.; Sakib, M S.; Kerimoglu, C. ; Krüger, D. M.; Kaurani, L. ; Islam, M. R. & Joshi, P. D. et al. (2021)
The EMBO Journal,. DOI: https://doi.org/10.15252/embj.2020106459
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Details
- Authors
- Michurina, Alexandra; Sakib, M Sadman; Kerimoglu, Cemil ; Krüger, Dennis Manfred; Kaurani, Lalit ; Islam, Md Rezaul; Joshi, Parth Devesh; Schröder, Sophie; Centeno, Tonatiuh Pena ; Zhou, Jiayin; Fischer, André
- Abstract
- In mammals, histone 3 lysine 4 methylation (H3K4me) is mediated by six different lysine methyltransferases. Among these enzymes, SETD1B (SET domain containing 1b) has been linked to syndromic intellectual disability in human subjects, but its role in the mammalian postnatal brain has not been studied yet. Here, we employ mice deficient for Setd1b in excitatory neurons of the postnatal forebrain, and combine neuron-specific ChIP-seq and RNA-seq approaches to elucidate its role in neuronal gene expression. We observe that Setd1b controls the expression of a set of genes with a broad H3K4me3 peak at their promoters, enriched for neuron-specific genes linked to learning and memory function. Comparative analyses in mice with conditional deletion of Kmt2a and Kmt2b histone methyltransferases show that SETD1B plays a more pronounced and potent role in regulating such genes. Moreover, postnatal loss of Setd1b leads to severe learning impairment, suggesting that SETD1B-dependent regulation of H3K4me levels in postnatal neurons is critical for cognitive function.
- Issue Date
- 2021
- Journal
- The EMBO Journal
- Project
- EXC 2067: Multiscale Bioimaging
SFB 1286: Quantitative Synaptologie
SFB 1286 | B06: Die Rolle von RNA in Synapsenphysiologie und Neurodegeneration - Working Group
- RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)
RG E. Zeisberg (Kardiales Stroma) - ISSN
- 0261-4189
- eISSN
- 1460-2075
- Language
- English