PT  - JOURNAL ARTICLE
AU  - Alexandra Michurina
AU  - M Sadman Sakib
AU  - Cemil Kerimoglu
AU  - Dennis Manfred Krüger
AU  - Lalit Kaurani
AU  - Md Rezaul Islam
AU  - Joshi Parth Devesh
AU  - Sophie Schröder
AU  - Tonatiuh Pena Centeno
AU  - Jiayin Zhou
AU  - Ranjit Pradhan
AU  - Julia Cha
AU  - Xingbo Xu
AU  - Gregor Eichele
AU  - Elisabeth M. Zeisberg
AU  - Andrea Kranz
AU  - A. Francis Stewart
AU  - Andre Fischer
TI  - Postnatal SETD1B is essential for learning and the regulation of neuronal plasticity genes
AID  - 10.1101/2021.08.02.454636
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.02.454636
4099  - http://biorxiv.org/content/early/2021/08/02/2021.08.02.454636.short
4100  - http://biorxiv.org/content/early/2021/08/02/2021.08.02.454636.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.