Histone-methyltransferase MLL2 (KMT2B) is required for memory formation in mice

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Cemil Kerimoglu - , University Medical Center Göttingen (Author)
  • Roberto C Agis-Balboa - , University Medical Center Göttingen (Author)
  • Andrea Kranz - , Chair of Applied Genomics (Author)
  • Roman Stilling - , University Medical Center Göttingen (Author)
  • Sanaz Bahari-Javan - , University Medical Center Göttingen (Author)
  • Eva Benito-Garagorri - , University Medical Center Göttingen, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Göttingen (Author)
  • Rashi Halder - , University Medical Center Göttingen, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Göttingen (Author)
  • Susanne Burkhardt - , University Medical Center Göttingen (Author)
  • Adrian Francis Stewart - , Chair of Applied Genomics (Author)
  • Andre Fischer - , University Medical Center Göttingen, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Göttingen (Author)

Abstract

The consolidation of long-term memories requires differential gene expression. Recent research has suggested that dynamic changes in chromatin structure play a role in regulating the gene expression program linked to memory formation. The contribution of histone methylation, an important regulatory mechanism of chromatin plasticity that is mediated by the counteracting activity of histone-methyltransferases and histone-demethylases, is, however, not well understood. Here we show that mice lacking the histone-methyltransferase myeloid/lymphoid or mixed-lineage leukemia 2 (mll2/kmt2b) gene in adult forebrain excitatory neurons display impaired hippocampus-dependent memory function. Consistent with the role of KMT2B in gene-activation DNA microarray analysis revealed that 152 genes were downregulated in the hippocampal dentate gyrus region of mice lacking kmt2b. Downregulated plasticity genes showed a specific deficit in histone 3 lysine 4 di- and trimethylation, while histone 3 lysine 4 monomethylation was not affected. Our data demonstrates that KMT2B mediates hippocampal histone 3 lysine 4 di- and trimethylation and is a critical player for memory formation.

Details

Original languageEnglish
Pages (from-to)3452-3464
Number of pages13
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume33
Issue number8
Publication statusPublished - 20 Feb 2013
Peer-reviewedYes

External IDs

PubMedCentral PMC6619533
ORCID /0000-0002-7481-0220/work/142247421
ORCID /0000-0002-4754-1707/work/142248081

Keywords

Keywords

  • Animals, DNA-Binding Proteins/deficiency, Hippocampus/enzymology, Histone Methyltransferases, Histone-Lysine N-Methyltransferase/deficiency, Maze Learning/physiology, Memory, Long-Term/physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Neoplasm Proteins/deficiency, Neuronal Plasticity/genetics