RT Journal Article
SR Electronic
T1 Postnatal SETD1B is essential for learning and the regulation of neuronal plasticity genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.02.454636
DO 10.1101/2021.08.02.454636
A1 Alexandra Michurina
A1 M Sadman Sakib
A1 Cemil Kerimoglu
A1 Dennis Manfred Krüger
A1 Lalit Kaurani
A1 Md Rezaul Islam
A1 Joshi Parth Devesh
A1 Sophie Schröder
A1 Tonatiuh Pena Centeno
A1 Jiayin Zhou
A1 Ranjit Pradhan
A1 Julia Cha
A1 Xingbo Xu
A1 Gregor Eichele
A1 Elisabeth M. Zeisberg
A1 Andrea Kranz
A1 A. Francis Stewart
A1 Andre Fischer
YR 2021
UL http://biorxiv.org/content/early/2021/08/02/2021.08.02.454636.abstract
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.