Year: 2021
Type: preprint
Abstract: ABSTRACT Histone 3 lysine 4 methylation (H3K4me) is mediated by six different lysine methyltransferases. Amongst these enzymes SET domain containing 1b (SETD1B) has been linked to syndromic intellectual disability but its role in the postnatal brain has not been studied yet. Here we employ mice that lack Setd1b from 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 genes with a broad H3K4me3 peak at their promoters that represent neuronal enriched genes linked to learning and memory function. Comparative analysis to corresponding data from conditional Kmt2a and Kmt2b knockout mice suggests that this function is specific to SETD1B. Moreover, postnatal loss of Setd1b leads to severe learning impairment, suggesting that SETD1B-mediated regulation of H3K4me levels in postnatal neurons is critical for cognitive function.
Authors: Alexandra Michurina, M Sadman Sakib, Cemil Kerimoglu, Dennis Manfred Krüger, Lalit Kaurani, Md Rezaul Islam, Joshi Parth Devesh, Sophie Schröder, Tonatiuh Pena Centeno, Jiayin Zhou, Ranjit Pradhan, Julia Cha, Xingbo Xu, Gregor Eichele, Elisabeth M. Zeisberg, Andrea Kranz, A. Francis Stewart, Andre Fischer
Institutions: German Center for Neurodegenerative Diseases, Max Planck Institute for Biophysical Chemistry, Universitätsmedizin Göttingen, German Centre for Cardiovascular Research, Multiscale Bioimaging, University of Göttingen, Biotechnologisches Zentrum, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Max Planck Institute of Molecular Cell Biology and Genetics
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: International Max Planck Research School for Environmental, Cellular and Molecular Microbiology, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Deutsches Zentrum für Neurodegenerative Erkrankungen, International Max Planck Research School for Advanced Methods in Process and Systems Engineering
OpenAlex ID: W3191774005